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Bacille Calmette-Guerin (BCG) Vaccine

Bacille Calmette-Guérin (BCG) Vaccine Clinical Trials, Dosage, Efficacy, Indications, Side Effects

In 1921, French scientists Albert Calmette and Camille Guérin developed the initial Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine. The BCG vaccine was designed to protect cattle from bovine tuberculosis and was administered to a newborn baby in Paris. BCG-induced whole-blood cytokine levels differ by age, vaccine formulation, and concentration. In addition, BCG-induced cytokine production correlated with CFU, suggesting that mycobacterial viability may contribute to BCG-induced immune responses. Mycobacterium tuberculosis (Mtb) is the etiological agent of tuberculosis (TB).

Since 1921, BCG vaccines have been administered approximately 4 billion times worldwide. BCG vaccines initially targeted against TB, tuberculosis meningitis, and non-specific protective effects against other respiratory tract infections and certain cancers. In naive adult populations, the BCG vaccine, administered as an intradermal injection, takes at least two years to achieve complete protection due to several off-target effects. A study published in September 2023 characterized the mechanisms of BCG revaccination-induced trained immunity (TI). Data highlights a balanced immune response comprising pro- and anti-inflammatory mediators, a feature of BCG revaccination-induced immunity. These immune responses have been used to prevent and treat various diseases, including bladder cancer, herpes, human papillomavirus, leprosy, and Buruli ulcers.

BCG immunization or MTB infection of the human body induces an increase in gene rearrangement and metabolism in intrinsic immune cells, such as macrophages, NK cells, and monocytes, leading to the increased secretion of cytokines, including TNF-α, IL-1β, and IL-6. During reinfection with other pathogens, such as HSV-1, these trained innate immune cells rapidly secrete TNF-α, IL-1β, IL-6, and other cytokines to eliminate invading pathogens.

A study reported in July 2024 found that the immune response to M. tuberculosis (Mtb) is associated with the activation of type 1 T helper (Th1) responses and the production of a range of cytokines, including tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). Genetic defects, such as mutations in cytokine receptors like interleukin-12 (IL-12) or IFN-γ, enhance the cell differentiation, leading to increased susceptibility to progressive mycobacterial disease. In addition, the neutralization of TNF-α by monoclonal antibodies (such as those used in treating rheumatoid arthritis) can prevent LTBI reactivation. 

On January 19, 2021, Dr. Camille Locht, research director at Inserm's Institut Pasteur de Lille, stated, "The BCG can train the cells of the innate immune system to make them more fit and active to fight against other diseases." The U.S. National Institutes of Health (NIH) says the BCG vaccine is safe. The BCG vaccine is used in many countries (Mexico, the U.K., Canada) for emerging therapeutic off-target benefits, such as treating bladder cancer. As of February 2023, the biological interaction between M. tuberculosis (Mtb) and the human host is complex and only partially understood, according to the World Health Organization (WHO). The WHO 2022 Report says BCG vaccination should continue for all infants soon after birth, except for those living with HIV in high tuberculosis-prevalence settings. The WHO adopted requirements for the BCG vaccine in 1965, and these were updated in 1978 to reflect the increased knowledge of vaccinations and the change to freeze-dried preparations. These were modified in 1985 to amend requirements concerning the expiry date. In its thirteenth report, the WHO Expert Committee on Biological Standardization considered formulating international requirements for manufacturing and controlling the BCG vaccine. On September 30, 2022, the WHO published consolidated guidelines on TB, Module 3. The WHO recommends BCG vaccination at birth in countries where tuberculosis is endemic. In 2024, the U.K.'s NHS states that the BCG vaccine will be particularly beneficial in protecting babies and young children against more severe forms of TB.

On August 5, 2022, new research (MIS BAIR) led by the Murdoch Children's Research Institute in Australia and published in the peer-reviewed Science Advances journal showed how BCG vaccination produces 'trained immunity responses' lasting more than 14 months after administration. On August 15, 2022, research findings published by the Cell Reports Medicine journal suggested that the BCG platform protects against infectious diseases and that vaccine efficacy takes 1-2 years to manifest, but the protection may last decades. The Rockefeller Foundation announced on September 20, 2022, that it would commit US$15 million to the Global Fund to Fight AIDS, TB, and Malaria.

BCG Vaccine United States

Merck TICE® BCG vaccine is an attenuated, strain tice live antigen preparation of Mycobacterium bovis. The TICE strain was developed at the University of Illinois from a strain originating at the Pasteur Institute. Since 2012, Merck & Co. has been the supplier of the TICE BCG vaccine in the U.S. Merck confirmed it was experiencing a global shortage due to the growing demand for BCG vaccines. In October 2020, Merck announced plans to construct a manufacturing facility in Durham, North Carolina, to expand production of the TICE BCG vaccine.

The U.S. Centers for Disease Control and Prevention (CDC) states that the BCG vaccine is not generally recommended for use in the U.S. due to the minimal risk of infection with Mycobacterium tuberculosis. The CDC recommends BCG vaccination only for children who have a negative tuberculin skin test and are at ongoing risk of exposure to tuberculosis. BCG vaccination may be recommended for older children who have an increased risk of developing TB, such as children who have recently arrived from countries with high levels of TB, including those in Africa, the Indian subcontinent, parts of southeast Asia, parts of South and Central America, and parts of the Middle East, and children who have come into close contact with somebody infected with respiratory TB. Many foreign-born persons have been BCG-vaccinated. BCG is used in many countries with a high prevalence of TB to prevent childhood tuberculous meningitis.

BCG Vaccines 2025

As of 2025, various BCG vaccines are available globally, including TUBERVAC-rBCG, BCG vaccine AJV (A.J. Vaccines), VERITY-BCG™, France BCG vaccine (Pasteur 1173P2), Brazil strain (BCG oral Mearou RJ), Bulgarian substrain (Sofia SL222), Japan 172 strain (Tokyo 172-1), and BCG-Denmark 133.

BCG Vaccination Benefits For Infants

A study published by the BMJ in September 2025 concluded that in newborn babies weighing <2000 g in intensive care, BCG-OPV administered at a median age of 0.9 days reduced all-cause neonatal mortality, owing to a decrease in deaths from infections other than tuberculosis.

BCG Vaccine Alzheimer's Disease Dementia

On August 24, 2023, a systematic review and meta-analysis of BCG administration on the risk of dementia in bladder cancer patients found the pooled HR was 0.55 (0.42–0.73), indicating that BCG exposure or treatment reduced the risk of incident dementia by 45%. The JAMA Network published an Original Investigation on May 19, 2023, led by investigators at Massachusetts General Hospital and Brigham and Women's Hospital. The investigation concluded that the BCG vaccine was associated with a significantly lower rate and risk of Alzheimer's disease and related dementia in a cohort of patients with bladder cancer when accounting for death as a competing event. This phase 2 clinical trial is ongoing.

A mini-review published on June 27, 2022, highlights how immune cells can mediate the relationship between BCG vaccination and AD, thereby supporting the health of the central nervous system. On February 22, 2022, MDPI published "BCG Vaccination and Plasma Amyloid: A Prospective, Pilot Study with Implications for Alzheimer's Disease," in which participants tended to have higher values of the Aβ42/Aβ40 ratio after receiving the BCG vaccine. On November 7, 2019, researchers at the Hadassah-Hebrew University Medical Centre collected the data of 1,371 people who had or had not received BCG as part of their treatment for bladder cancer. They found that just 2.4% of the patients treated with BCG developed Alzheimer's over the following eight years, compared with 8.9% of those not given the vaccine.

BCG Vaccine Bladder Cancer

The study of BCG anti-tumor activity began in 1929. Since 1977, BCG vaccination has been the standard therapy for treating high-risk nonmuscle-invasive bladder cancer (NMIBC) patients to avoid the recurrence and progression of the disease. BCG is the most common intravesical immunotherapy for treating early-stage bladder cancer, according to Cancer.org. BCG vaccination induces the recruitment and polarization of macrophages towards a pro-inflammatory phenotype, accompanied by the induction of the inflammatory cytokines TNF-α, IL-1β, and IL-6 in the tumor microenvironment. Macrophages directly induced apoptosis of human cancer cells through zebrafish TNF signaling.

Serum Institute of India's BCG vaccine is exported to Canada for immunotherapy to treat bladder cancer. In Australia, intravesical immunotherapy with BCG is approved. On April 22, 2024, the U.S. FDA approved the multi-dose ANKTIVA for BCG-unresponsive non-muscle Invasive Bladder Cancer. The End Drug Shortages Alliance confirmed in 2023 that about 20% of the organizations were not providing complete BCG vaccination routines to eligible cancer patients. When comparing BCG strains, the Tice stain showed a relatively high probability of recurrence compared with the Connaught (RR, 1.29; 95% CI 1.01–1.64) and RIVM (RR, 2.04; 95% CI 1.28–3.25) strains.

BCG Vaccine Diabetes

Various studies are investigating whether BCG vaccine therapy can enhance blood sugar control in Type 1 Diabetes by altering metabolism. In January 2023, PLOS ONE published the results of two observational studies. The epidemiological evidence analyzed here suggests that BCG may play a role in the prevention of type 1 diabetes (T1D) but does not support its role in preventing type 2 diabetes (T2D), most likely due to the interference of metformin. Our ecological analysis of global data suggests a potential role for neonatal BCG in preventing type 1 diabetes (T1D) and, to a lesser extent, type 2 diabetes (T2D). Researchers from Massachusetts General Hospital (MGH) presented positive updates in 2021 on their trials of the BCG vaccine, which aim to safely and significantly lower blood sugar levels. Over the course of three years, BCG restores the gene expression pattern of Tregs in type 1 diabetics to a pattern consistent with that of non-type one control subjects. In June 2018, an MGH research team published in npj Vaccines that three years after receiving two administrations of the BCG vaccine, four weeks apart, all members of a group of adults with longstanding type 1 diabetes showed an improvement in HbA1c to near-normal levels. This improvement persisted for the following five years.

BCG Vaccine Eczema

The Murdoch Children's Research Institute's initial study findings, published in the journal Allergy on August 24, 2021, showed that the BCG vaccine had a modest beneficial effect in preventing eczema in high-risk infants. However, a single dose of BCG-Denmark soon after birth could reduce the incidence of eczema in infants with two atopic parents.

BCG Vaccination Endometriosis

A mini-review published in 2021 addresses the possible use of BCG as a therapeutic for endometriosis, a syndrome of chronic pelvic pain due to ectopic growth of endometrial-type tissue outside of the uterine lining. The immune response to endometriosis reveals a complex balance between systemic pro-inflammatory immune activation and local anti-inflammatory characteristics that permit tumor growth. Lesions of endometriosis have an immune-cell-rich stroma with aberrant expression of pro- and anti-inflammatory cytokines, including IL-16, IL-18, and IL-1. BCG vaccination has been shown to alter the secretion of pro-inflammatory cytokines.

BCG Vaccine Herpes

The Lancet's eClinicalMedicine published results from a phase 3 clinical trial conducted across multiple countries on October 16, 2023, assessing the impact of BCG vaccination on recurrent herpes labialis. The study's results suggest that BCG-induced non-specific immune responses can enhance the body's immune response, particularly in males with a history of frequent recurrences. 

A systematic review of Medline, EMBASE, and PubMed in June 2020 identified 16 articles that were deemed relevant, comprising eight animal and eight human studies (301 patients). In nonrandomized human studies (that failed to control for a placebo effect), BCG vaccination appeared beneficial in 78% of adults with recurrent herpes genitalis or labialis, with 37% being recurrence-free for an extended period, 41% experiencing less frequent or severe episodes, and only 22% reporting no change. In the two studies on recurrent herpes labialis, 94% appeared to benefit from BCG. The one randomized controlled trial used an intervention in the control group with immunomodulatory effects, which limited its interpretation. In conclusion, the BCG vaccine is a readily available vaccine candidate that can help decrease diseases associated with HSV infection.

BCG Vaccine HIV

Coinfection with Mtb and HIV is a lethal combination, says the WHO. In sub-Saharan Africa, where HIV is most prevalent, the annual incidence of TB has risen to more than 300 cases per 100,000 inhabitants. In some of these places, nearly 50% of the HIV-infected population is coinfected with TB, and more than two-thirds of TB patients are infected with HIV. The lifetime risk of developing TB is as high as 30-50% for HIV-infected persons. In some parts of Southeast Asia, an estimated 20-25% of TB cases will be directly attributable to HIV, according to the WHO.

For neonates born to mothers with an unknown HIV status and neonates with an unknown HIV status born to HIV-infected mothers (regardless of their ART status), the WHO recommends BCG vaccination, as the benefits outweigh the risks. For a neonate confirmed by virologic testing to be positive for HIV, it is recommended that BCG vaccination be delayed until ART has been started.

Experts at Fred Hutchinson Cancer Center suggested in a study published in The Lancet HIV on October 11, 2022, that future TB vaccine development clinical trials should ensure people living with HIV have access to safe and effective TB vaccines.

On June 27, 2022, The Lancet Infectious Diseases published the results from a phase 2 study on HIV-infected children in South Africa. The researchers' Interpretation: The VPM1002 vaccine candidate was less reactive than BCG and was not associated with serious safety concerns. Both vaccines were immunogenic, with higher responses to the BCG vaccine.

In October 2020, the journal Nature published a BCG vaccine review that stated 'the potential TB vaccine candidates that can be exploited for use as a dual vaccine against TB/HIV copandemic (ii) progress made in the realm of TB/HIV dual vaccine candidates in a small animal model, NHP model, and human clinical trials the failures and promising targets for a successful vaccine strategy while delineating the correlates of vaccine-induced protection.'

BCG Vaccine Leprosy

Repeat BCG vaccination is standard practice in many countries to prevent Hansen's disease (leprosy). In 2018, the WHO included leprosy in its recommendation for single-dose BCG vaccination.

BCG Vaccine Liver Cancer Tumors

A study published in Advanced Science by UC Davis Health in February 2024 found that a dose of the BCG vaccine reduced liver tumor burden and extended the survival of mice with liver cancer. The study is the first to show BCG vaccinations as a potential treatment for hepatocellular carcinoma, a condition often associated with unfavorable treatment outcomes. Vaccination was characterized by a favorable safety profile and efficacy in inhibiting fibrosis, improving metabolism, and engaging trained immunity and T cells in therapeutic mechanisms.

BCG Vaccine Tuberculosis

Tuberculosis (TB) is a vaccine-preventable disease, says the WHO. A study titled "Efficacy of BCG Vaccine in the Prevention of Tuberculosis: Meta-analysis of the Published Literature" was published in 1994. On January 24, 2023, PLOS Medicine published a research article titled "The Cost and Cost-Effectiveness of Novel Tuberculosis Vaccines in Low- and Middle-Income Countries: A Modeling Study." Our analysis projected that an effective new TB vaccine could offer significant health and economic benefits from 2028 to 2050. The Lancet published an early-release survey on August 10, 2022 - Infant BCG vaccination and risk of pulmonary and extrapulmonary TB throughout the life course: a systematic review and individual participant data meta-analysis. Interpretation: Our results suggest that BCG vaccination at birth prevents tuberculosis in young children but is ineffective in adolescents and adults. Immunoprotection, therefore, needs to be boosted in older populations.

The WHO's Global Tuberculosis Report 2024 highlights mixed progress in the global fight against TB. While the number of TB-related deaths decreased from 1.32 million in 2022 to 1.25 million in 2023, the total number of people falling ill with TB rose slightly to an estimated 10.8 million in 2023.

BCG Vaccine Yellow Fever

The study demonstrated the effects of BCG vaccination on genome-wide histone modifications induced in trained monocytes. These modifications are associated with reduced yellow fever virus viremia levels due to increased IL-1β production and release.

BCG Vaccine for Children

BCG vaccination at birth or in infancy significantly reduces the risk of TB. The potential implications for child health are substantial, according to a study published in October 2020. For example, if BCG vaccination were given to children at birth, if higher measles vaccination coverage could be obtained, if diphtheria, tetanus, and pertussis-containing vaccines were not provided with or after the measles vaccine, or if the BCG strain with the best non-specific effects could be used consistently, then child mortality could be considerably lower. In 2005, all EU countries, including Andorra, Bulgaria, Norway, Romania, and Switzerland, participated in a survey on BCG vaccination in children. 

BCG Vaccine Pregnancy

BCG vaccination should not be given during pregnancy. However, no harmful effects on the fetus have been observed, and further studies are needed to prove its safety.

BCG Vaccine Dosage

In its thirteenth report, the WHO Expert Committee first considered establishing international requirements for the manufacture and control of the BCG vaccine in the context of Biological Standardization. Approved dose: BCG vaccine can be given either cutaneously or intradermally. Research is currently being conducted on respiratory administration, as humans' natural infection and sensitization to Mycobacterium tuberculosis typically occur in the respiratory system. The timing and dose of BCG vaccination were assessed by the 1995 Tuberculin Vaccination Survey (US FDA), Medline.gov, the U.K., 2020, and WHO. The intact vials of BCG VACCINE should be stored refrigerated at 2–8°C (36–46°F). This agent contains live bacteria and should be protected from direct exposure to the environment. When used to protect against TB, BCG is injected into the skin. Keep the vaccination area dry for 24 hours after receiving the vaccination, and keep it clean until the vaccination area is indistinguishable from the surrounding skin.

BCG Vaccine Side Effects

If you experience any unusual or severe symptoms after receiving this vaccine, tell your healthcare provider promptly or report them to the Vaccine Adverse Event Reporting System at www.vaers.hhs.gov.

BCG Vaccine United Kingdom

In the U.K. and various countries, BCG vaccination is administered to newborn infants at risk of TB. The WHO suggests that BCG programs for different age groups are equally effective against TB during puberty. BCG vaccines have effectively protected children against the rarer, severe forms of TB, such as TB meningitis. The Lancet Global Health published a study in September 2022 that found that BCG vaccination at birth protects against TB among children under five.

Public Health England (PHE) announced on July 27, 2021, that eligible babies should be offered the BCG vaccine at 28 days of age or soon after. BCG vaccination is recommended for babies up to 1 year old, and BCG vaccination may also be recommended for older children who have an increased risk of developing TB. On September 15, 2021, the U.K.'s PHE updated its fact sheet, which had previously been published in The Lancet on September 7, 2021, and in Cancer Immunology on June 24, 2022. Epidemiologist   Christine Stabell Benn and colleagues found (Mar. 2012) that BCG administered to children with low birth weight reduced all-cause mortality in these children by about 40% in the first year of life.

BCG Vaccine Price

UNICEF data show that the price awarded for the BCG vaccine per dose is nominal. The U.S. CDC Vaccine Price List was last updated in December 2022; many pharmacies in the U.S. charge over $100.00 for a single vial of BCG vaccines. According to various reports, the global TB Vaccine revenue is expected to increase by over 3% annually by 2027. Additional information on the BCG vaccine discount is posted at InstantRx™.

BCG Vaccine Clinical Trials

BCG is currently involved in active clinical trials covering various conditions. Click here to review the various ongoing clinical trials. 

0 min read
Manufacturer: 
Merck
Reviewer: 
Robert Carlson, MD
Vaccine: 
Bacille Calmette-Guerin (BCG) Vaccine
VIS: 
PDF
Availability: 
200 countries
Generic: 
Bacille Calmette-Guerin
Clinical Trial: 
https://clinicaltrials.gov/
Drug Class: 
Attenuated Vaccine
Find Price: 
Discounts
Clinical Trial Phase I: 
Clinical Trials Using BCG Vaccine
Clinical Trial Phase II: 
Vaccination to Protect Healthcare Workers Against COVID-19
Clinical Trial Phase III: 
BCG Vaccination against Infection in the Elderly
Clinical Trial Phase IV: 
BRACE trial is now the world's largest study on the off-target effects of the BCG vaccine
Lab Test: 
CDC Guidelines
Condition: 
Tuberculosis
Availability Link: 
Current and past BCG vaccination policies and practices for over 200 count
Last Reviewed: 
Friday, December 12, 2025 - 09:25
Brand: 
BCG
Abbreviation: 
BCG
CPT Code: 
90585
ChEMBL ID: 
2108905
Accession Number: 
DB12768
Status: 
Approved
Manufacturer Country ID: 
US
FDA First In Class: 
Yes
Kosher: 
Yes
Halal: 
Yes
Side Effects: 
BCG side effects
Ingredients: 
BCG ingredients
Countries: 
U.S.
Canada
India
Europe
UK
Brazil
Japan
Australia
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TG4001 HPV Cancer Vaccine

TG4001 HPV Vaccine Description

TG4001 is a therapeutic cancer vaccine candidate based on an attenuated and modified poxvirus (MVA) as a vector expressing the HPV16 E6 and E7 proteins (rendered non-oncogenic) interleukin-2, made by a type of T lymphocyte. TG4001 is developed in Human Papillomavirus (HPV)16 positive cancers, such as cervical, vaginal, and oropharyngeal squamous cell carcinoma of the head and neck. Transgene's myvac® is designed to stimulate and educate the patient's immune system to recognize and destroy tumors using their cancer-specific genetic mutations. 

On September 16, 2020, Transgene, previously known as Tipapkinogen Sovacivec, announced the analysis of the efficacy data from the Phase 1b/2 trial combining TG4001 with avelumab in HPV16-positive recurrent and/or metastatic malignancies showed promising clinical activity in the overall study population (34 evaluable patients).

Transgene announced on November 2, 2022, following an interim analysis of its randomized controlled Phase II clinical study comparing TG4001 in combination with avelumab to avelumab alone in patients with HPV16-positive anogenital tumors, the Independent Data Monitoring Committee has recommended the study continue. Based on positive signals observed in the interim analysis, the trial is expected to enroll an additional 66 patients for a total trial size of 120 patients compared to the previously announced target of 150 patients.

On June 5, 2023, the Company announced data from a phase 2 clinical trial found TG4001 could induce de novo immune responses against HPV16 antigens E6 and E7 in patients with advanced HPV16-positive anogenital cancers, and patients with complete objective response showed strong vaccine-induced immunoreactivity. Furthermore, Transgene announced on June 6, 2023, new immunological data assessed by tetramer staining confirms the induction of T cell responses in treated patients, all trial patients treated with TG4050 monotherapy continue to remain in remission to date. and Transgene and NEC are preparing a Phase II trial to further demonstrate the potential of TG4050 as an adjuvant treatment of head and neck cancer.

Transgene is a France-based clinical-stage biotechnology company that designs and develops novel immunotherapeutics.

TG4001 HPV Vaccine Indication

TG4001 is indicated to treat HPV16+ recurrent or metastatic malignancies, including oropharyngeal cancers. Therapeutic vaccines are active and targeted immunotherapeutics. According to the Company, they induce a cascade of immune reactions that produce T cells that will only destroy specific malignant cells.

TG4001 HPV Vaccine Dosage

Dosing levels are being evaluated in ongoing clinical trials. TG4001 is designed to have a two-pronged antiviral approach: to alert the immune system specifically to cells presenting the HPV16 E6 and E7 antigens found in HPV16-related tumors and to further stimulate the infection-clearing activity of the immune system through interleukin 2 (IL-2). 

TG4001 HPV Vaccine News

June 6, 2023 - Alessandro Riva, Chairman and CEO of Transgene, commented, "TG4050 has demonstrated its potential to extend patient remission after surgery and firmly establishes Transgene among the leading pioneers in the emerging field of individualized cancer vaccines. The monotherapy data we present at ASCO are a solid basis to accelerate the clinical development of this innovative therapy as an adjuvant treatment to HPV-negative head and neck carcinoma and potentially in other indications."

June 5, 2023 - Transgene announced that new data confirm the ability of this novel investigational therapeutic cancer vaccine to induce immune responses against HPV16 antigens that are associated with anti-tumor response.

November 2, 2022 - Hedi Ben Brahim, Chief Executive Officer of Transgene, stated: "The IDMC's recommendation to continue the study reinforces our confidence in TG4001, which follows promising data from our earlier Phase Ib/II trial. This also enables us to reduce the number of randomized patients in the trial. We look forward to completing this trial in H1 2024 and communicating its results when available."

June 24, 2021 - Transgene announced that the first patient had been enrolled in a randomized, controlled Phase II study evaluating the combination of TG4001 with avelumab versus avelumab monotherapy in patients with HPV16-positive anogenital tumors.

March 10, 2021 - Transgene announced the initial Phase Ib/II trial conducted in France and Spain had been amended to include a randomized comparison of TG4001 with avelumab versus avelumab monotherapy in anogenital cancers. The submission of the amended protocol has been initiated in Europe. Also, Transgene received US FDA clearance for the protocol under TG4001 IND. Patient enrollment is expected to start in Q2 2021. The trial will focus on patients with recurrent or metastatic HPV16-positive anogenital cancer without liver metastases, including cervical, vulvar, vaginal, penile, and anal cancer.

October 27, 2020 - Transgene is communicating the content of the late-breaking poster abstract that will be presented at the SITC 35th Anniversary Annual Meeting (SITC 2020), to be held virtually November 9-14, 2020. The combination of TG4001 and avelumab demonstrates anti-tumor activity (23.5% ORR) in patients with previously treated recurrent and/or metastatic HPV-related cancers. In addition, liver metastases profoundly impact outcomes regarding ORR and PFS. In patients without liver metastases, an ORR of 34.8% and a median PFS of 5.6 months were achieved.

October 19, 2020 - Transgene announced that detailed results of the data from the Phase 1b/2 trial combining TG4001 would be presented in a poster presentation at the upcoming virtual meeting of the Society for Immunotherapy of Cancer taking place November 9-14, 2020.

July 22, 2020 - Transgene performed a pooled analysis of the data from the Phase 1b/2 trial combining TG4001. This analysis confirms that TG4001 can be safely combined with an immune checkpoint inhibitor and shows the clinical activity of this combination regimen. The trial is being conducted in collaboration with Merck KGaA, Darmstadt, Germany, and Pfizer.

September 30, 2019 - Transgene presented promising safety and efficacy data of TG4001 in combination with avelumab (BAVENCIO®), a human anti-programmed death-ligand (PD-L1) antibody, in Human Papillomavirus (HPV) 16+ recurrent or metastatic malignancies, including oropharyngeal cancers.

April 4, 2019 - Study: Tipapkinogen Sovacivec therapeutic HPV vaccine's efficacy and safety in cervical intraepithelial neoplasia grades 2 and 3: Randomized controlled phase II trial with 2.5 years of follow-up.

TG4001 HPV Cancer Vaccine Clinical Trials

The Phase II study evaluates TG4001, an investigational therapeutic cancer vaccine, combined with avelumab compared to avelumab alone in patients with HPV16-positive anogenital tumors without liver metastases, through a continuing collaboration with the alliance of Merck KGaA, Darmstadt, Germany, and Pfizer, which is supplying avelumab.

Clinical Trial NCT03260023:  Phase Ib/II of TG4001 and Avelumab in HPV16 Positive R/M Cancers Including Oropharyngeal SCCHN.

Clinical Trial NCT01022346: A Study of RO5217790 in Participants With High-Grade Cervical Intraepithelial Neoplasia Associated With High-Risk Human Papillomavirus (HR-HPV) Infection (Completed).

0 min read
Manufacturer: 
Transgene
Reviewer: 
Robert Carlson, MD
Holly Lutmer PharmD
Vaccine: 
TG4001 HPV Cancer Vaccine
VIS: 
PDF
Availability: 
TBD
Generic: 
TG4001
Drug Class: 
Therapeutic Vaccine
Clinical Trial Phase I: 
Phase Ib/II of TG4001 and Avelumab in HPV16 Positive R/M Cancers Including Oropharyngeal SCCHN
Clinical Trial Phase II: 
A Study of RO5217790 in Participants With High Grade Cervical Intraepithelial Neoplasia (CIN) Associated With High Risk HPV
Lab Test: 
CDC
Condition: 
HPV Cancers
Last Reviewed: 
Tuesday, June 6, 2023 - 13:55
Accession Number: 
DB06239
Status: 
Candidate
Manufacturer Country ID: 
FR
Side Effects: 
Phase 2
Countries: 
France

Norovirus Oral Bivalent Vaccine

Vaxart Oral Pill Bivalent Norovirus Vaccine Clinical Trials, Dosage, Indication, News, Side Effects

Vaxart Inc.'s GI.1/GII.4 oral pill bivalent norovirus vaccine candidate, consisting of monovalent GII.4 VXA-G2.4-NS and GI.1 VXA-G1.1-NN, is designed to prevent illness from norovirus, a very contagious virus that causes vomiting and diarrhea. Norovirus GI.1 Norwalk VP1 Vaccine (VXA-G1.1-NN), an Oral E1/E3-Deleted Replication-Defective Recombinant Adenovirus serotype 5 with double-stranded ribonucleic acid (dsRNA) Adjuvant. The vaccine vector encodes for a full-length VP1 gene from the Norwalk virus (NV). The adjuvant is a short hairpin RNA (shRNA), expressed as a 21-nucleotide sequence (GAAACGA TATGGGCTGAATAC) in tandem, with the forward and reverse orientations separated by six nucleotides that comprise the loop of the RNA. The final drug product is formulated into an enteric-coated tablet. Vaxart's vaccine is differentiated from other norovirus candidates because it generates both systemic and mucosal immunity, delivered through the mouth, and is stable at room temperature.

Vaxart reported topline data from the Phase 1 clinical trial, which focused on lactating mothers, on April 30, 2024. In the breast milk of lactating mothers who received the Vaxart vaccine candidate in the high-dose group, antibodies to norovirus increased on average fourfold for the G1.1 virus strain and sixfold for the GII.4 virus strain. There were no vaccine-related serious adverse events, and no dose-limiting pharmacotoxicity was observed.

On March 6, 2025, Vaxart announced that data from the Phase 1b trial in elderly adults (55-80 years), which show strong and durable antibody responses and induction of norovirus-specific antibody and T cell responses, support the vaccine candidate's immunogenicity in a patient population that often has age-related reductions in immune reactions to injected vaccines. On May 14, 2025, Vaxart announced the publication of complete data from a Phase 2b challenge study of its first-generation oral pill norovirus vaccine candidate (NCT05212168) in Science Translational Medicine. Consistent with preliminary data reported in September 2023, the complete results show that the trial met five of its six primary endpoints and demonstrate the safety, efficacy, and immunogenicity of the vaccine candidate. Additional data included in the current publication include results from machine learning analyses that identify functional blocking antibody and fecal IgA as robust correlates of protection. These additional results will help inform the development of the Company’s second-generation oral pill norovirus vaccine candidate.

South San Francisco, CA-based Vaxart Inc. is a clinical-stage biotechnology company developing a range of oral recombinant vaccines based on its proprietary delivery platform. Vaxart believes that a vaccine that produces mucosal antibodies locally in the intestine and systemic antibodies circulating in the blood may offer better protection against norovirus infection than an injectable vaccine.

Vaxart Oral Bivalent Norovirus Vaccine Indication

Norovirus is the leading cause of acute viral gastroenteritis in all age groups in the United States. Approximately 3 million parents are forced to miss work, on average, 2.2 days, due to norovirus infections, to care for their children. The annual disease burden from norovirus in the U.S. alone is $10.6 billion. Globally, norovirus has become the leading cause of pediatric gastroenteritis in healthcare settings in countries that have adopted a rotavirus vaccine program.

Vaxart Oral Bivalent Norovirus Vaccine Dose

Dose: The vaccine was administered orally at three dose levels, with a prime and boost regimen 28 days apart. 

Vaxart Oral Bivalent Norovirus Vaccine Adverse Events

The Phase 2 dose-ranging study also demonstrated that the bivalent norovirus vaccine candidate was well tolerated, with a favorable safety profile that included no vaccine-related serious adverse events and no dose-limiting toxicity. The Phase 1b study found the vaccine was safe and well-tolerated in older adults. All solicited events were mild to moderate, with no grade 3 events related to the vaccine. Headache (14%) and malaise/fatigue (16%) were the most commonly solicited symptoms reported in the week following vaccine administration; headache (14%) and malaise/fatigue (14%) were reported at similar rates in the placebo group.

Vaxart Oral Bivalent Norovirus Vaccine News

March 6, 2025 - "A key finding of this study evaluating our first-generation oral pill norovirus vaccine candidate in elderly individuals was that the antibody and serum responses observed in these participants were robust and durable, and a cross-study analysis suggested that the observed antibody and cellular responses were independent of age. These findings are encouraging given that older adults have an increased risk of norovirus-related morbidity and may have less robust immune responses following vaccination than younger individuals," said James F. Cummings, MD, Chief Medical Officer at Vaxart. "Another key result was that an orally-administered vaccine can generate potent antibody responses in mucosal tissues outside the gastrointestinal tract, which could have important implications for use of our vaccine platform for norovirus and other indications."

April 30, 2024 - Dr. James F. Cummings, a Medical Officer, commented in a press release: "It can be difficult to immunize the youngest children mucosally because the immune system is still developing. Passive transfer of antibodies from mothers to infants via breast milk is potentially an innovative approach to improve infection resistance in infants."

December 21, 2023 - "This is an important step forward as we drive toward a vaccine candidate that may make it possible for mothers to protect their children against this highly contagious – and potentially lethal- virus. We look forward to announcing topline data from this study by the end of 2024," said Dr. James F. Cummings, Vaxart's Chief Medical Officer.

November 2, 2023: Dr. James F. Cummings, Vaxart's chief medical officer, comments, "We believe an oral norovirus vaccine pill may one day allow mothers to protect their infants against this highly contagious virus for which no approved vaccine is currently available."

September 6, 2023 - Challenge studies use higher quantities of virus than an individual may encounter during a naturally occurring infection. Yet, our vaccine candidate demonstrated a significant effect on infection and viral shedding, even though it did not achieve a statistically significant reduction in norovirus AGE," said Dr. James F. Cummings.

Vaxart Oral Bivalent Norovirus VXA-G1.1-NN Clinical Trials

A Phase 1, multicenter, randomized, double-blind, placebo-controlled, single-dose, dose-ranging study is designed to evaluate the safety, tolerability, and immunogenicity of an orally administered bivalent GI.1/GII.4 norovirus vaccine in healthy lactating females aged 18 years or older and their breast-feeding infants (aged 30 days to 11 months). The study is expected to enroll approximately 76 subjects at seven sites in South Africa. Subjects will be randomized into one of three groups: high-dose vaccine (N = 30), low-dose vaccine (N = 30), or placebo (N = 16).

This is a phase 2b randomized, double-masked, placebo-controlled vaccination and challenge study to assess the protective efficacy of the Vaxart Norovirus vaccine (VXA-G1.1-NN). Healthy adults will be randomized in a 1:1 ratio to receive one oral dose of vaccine or placebo.

Clinical Trial NCT03897309: Safety & Immunogenicity Study of Ad5 Based Oral Norovirus Vaccines (VXA-NVV-103)

Clinical Trial NCT02868073:  Phase 1 Placebo-controlled, Randomized Trial of an Adenoviral-vector Based Norovirus Vaccine (Completed)

Clinical Trial NCT03125473: Dose-Optimization Trial of VXA-G1.1-NN in Healthy Volunteers (Completed).

0 min read
Manufacturer: 
Vaxart
Reviewer: 
Robert Carlson, MD
Vaccine: 
Norovirus Oral Bivalent Vaccine
Availability: 
N/A
Generic: 
VXA-G1.1-NN
Drug Class: 
Vaccine
Clinical Trial Phase I: 
Safety & Immunogenicity Study of Ad5 Based Oral Norovirus Vaccines (VXA-NVV-103)
Clinical Trial Phase II: 
Safety and Immunogenicity of Bivalent GI.1 and GII.4 Vaccines
Condition: 
Norovirus
Last Reviewed: 
Saturday, May 31, 2025 - 12:40
Brand: 
Vaxart Monovalent Oral Tablet Vaccine
Status: 
Candidate
Manufacturer Country ID: 
US
FDA First In Class: 
Yes
Side Effects: 
Phase 1 study

Amezosvatein Shingles Vaccine

Amezosvatein CRV-101 Shingles Vaccine Clinical Trials, Dosage, Indication, Side Effects

Curevo Vaccine's Amezosvatein (CRV-101) for shingles is an adjuvanted subunit vaccine candidate designed to maximize cell-mediated immunity (CMI) protection by combining the gE protein antigen with our proprietary adjuvant. CRV-101 strategy contrasts with traditional approaches using live-killed or attenuated viruses. Sub-unit vaccines do not contain virus components and cannot cause infection. Additionally, the adjuvant component was specifically engineered to produce an optional immune response using a smaller amount of adjuvant with a targeted structure-function approach.

CRV-101 was designed to produce an optimal immune response while using a smaller amount of adjuvant to achieve similar efficacy but with fewer side effects than the currently approved shingles vaccine. CRV-101 enjoys a highly scalable, straightforward manufacturing profile explicitly designed to eliminate the potential for supply disruptions.

In the Phase 1 program, CRV-101 demonstrated robust immunogenicity as measured by humoral and cellular responses, with no grade 3 injection site reactions and a low (1.3%) grade 3 systemic side effects rate.

On January 7, 2024, the Company announced that Amezosvatein met all primary endpoints in the randomized, controlled, observer-blind Phase 2 trial, demonstrating non-inferiority to Shingrix as measured by humoral immune response. Amezosvatein also exhibited lower solicited local and systemic adverse event rates in this Phase 2 trial. The co-primary endpoint of the Phase 2 trial was humoral immune responses one month after the second vaccine dose (Day 84). This primary immunogenicity endpoint was met as participants' immune responses to amezosvatein were non-inferior to participants' immune responses to Shingrix. Additionally, amezosvatein's vaccine response rate was 100.0% compared to Shingrix's 97.9%. The co-primary safety endpoint was also met, with amezosvatein demonstrating lower rates of solicited local and systemic adverse events in this Phase 2 trial. The phase study's primary complete date is 2025-03-31.

Curevo is a Bothell, WA-based, privately-based, clinical-stage Company with partners in South Korea's Mogam Institute for Biomedical Research and GC Pharma. Curevo is dedicated to reducing the burden of infectious diseases by developing vaccines with improved tolerability and accessibility. On March 17, 2025, Curevo Vaccine announced the closing of a $110 million Series B round to advance the development of Amezosvatein. RA Capital Management led the Series A round. Other investors include Adjuvant Capital, Janus Henderson Investors, EN Investment, and founding investor GC Pharma. For more information, please visit www.curevovaccine.com. 'Amezosvatein' is the assigned non-proprietary name for CRV-101.

Amezosvatein CRV-101 Vaccine Indication

Once children are infected with chickenpox, the Varicella Zoster Virus (VZV) remains in the sensory ganglia, says the U.S. CDC. VZV typically remains inactive and reactivates to cause shingles with age-related immunosenescence. The CRV-101 vaccine candidate is currently indicated to prevent shingles in adults 50 and older.

Amezosvatein CRV-101 Vaccine Side Effects

The CRV-101 Phase 1 study included 90 subjects. The solicited reactogenicity adverse events consisted of no grade 3 local injection site events and only one grade 3 systemic event (fever) in the highest dose group. According to the U.S. CDC website, about 16 of those receiving Shingrix® experienced side effects that prevented them from participating in regular activities.

Amezosvatein CRV-101 Vaccine Dosage

In Phase 1, Group 1 Subjects receive two doses of the candidate CRV-101 formulation 1, administered intramuscularly (IM) in the deltoid region of the non-dominant arm, according to a 0, 2-month schedule. Group 2 Subjects receive two doses of the candidate CRV-101 formulation 2, administered intramuscularly (IM) in the deltoid region of the non-dominant arm, according to a 0, 2-month schedule. Furthermore, Groups 3 and 4 received increasing doses.

Amezosvatein CRV-101 Vaccine News

March 17, 2025 - Moncef Slaoui, PhD, will join Curevo Vaccines as Board Chair.

January 12, 2025: Curevo's CEO George Simeon commented, "Past experience shows that a comparable vaccine entering a market tends to split a share with the incumbent vaccine. However, history also shows that vaccines with better tolerability, like amezosvatein, which has demonstrated better tolerability compared to Shingrix in our Phase 2 trial, can capture dominant market share."

January 7, 2024 - "Fewer than 5% of eligible adults in most European countries and China have received both doses of Shingrix," noted George Simeon, Curevo's Chief Executive Officer, "and two-thirds of adults in the USA still need to be immunized against shingles. The market opportunity in shingles is large and underserved, with only a small fraction of the over $350 billion global addressable market currently vaccinated. The entire Curevo team is dedicated to swiftly bringing amezosvatein to global markets." 

November 16, 2022 - Curevo Vaccine announced the closing of a $26 million Series A1 financing round.

September 15, 2022 - Curevo Vaccine announced the completion of enrollment in a Phase 2b trial of their CRV-101 subunit vaccine to prevent the reactivation of the varicella-zoster virus in older adults. 

February 10, 2022 - Curevo Vaccine announced the closing of a $60 million Series A financing round.

March 18, 2021: Curevo Vaccine announced that approval was granted to move forward with a Phase 1b pediatric clinical trial in South Africa to evaluate the safety, efficacy, and immunogenicity of its non-live investigational vaccine CRV-101 against varicella (chickenpox) in immunocompromised pediatric HIV-infected populations. In November 2020, Curevo Vaccine submitted its clinical trial application to the South African Health Products Regulatory Authority, an entity of the South African Government's National Health Department.

September 15, 2020 - Curevo Vaccine announced antibody response data from its completed Phase 1 study investigating the safety, tolerability, and immune system response of CRV-101 in several formulations.

September 26, 2019 - Curevo, Inc. announced encouraging preliminary Phase I safety and tolerability results of their Shingles vaccine candidate, CRV-101. Interim trial results demonstrating the vaccine's promising safety and tolerability profile in 90 healthy adults ≥18 to <50 were presented in an oral presentation at the 44th annual International Herpesvirus Workshop in Knoxville, Tennessee.

November 5, 2018 - Curevo announced that the U.S. FDA had advanced the Company's Investigational New Drug application for CRV-101.

CRV-101 Clinical Trials

The Phase 2 trial (NCT05304351) enrolled 876 participants to receive either amezosvatein or Shingrix on an identical two-dose, two-month-apart schedule. Eight hundred seventy-six participants were randomized to receive one of four different amezosvatein doses or Shingrix. The mean follow-up of the 619 participants receiving amezosvatein was 18.8 months. The mean follow-up of the 257 participants who received Shingrix was 21.5 months. The trial's co-primary endpoints were anti-gE antibody humoral immune responses one month after the second vaccine dose (Day 84) and safety/reactogenicity. The randomized, observer-blind, and active-controlled trial was conducted at multiple centers in the USA. All suspected cases of shingles were confirmed by either PCR test or, if PCR testing was inconclusive or unavailable, by a blinded panel of shingles experts – a system similar to one used in multiple prior shingles vaccine pivotal studies. Day 421 measures were prospectively defined secondary outcomes measures.

Vaccines are studied for both safety and reactogenicity/tolerability. Data on the reactogenicity/tolerability of amezosvatein and Shingrix were collected via a participant diary for seven days after each injection. Participants were asked to grade the tolerability of each vaccine on a scale of 1 to 3. Grade 1 represents normal reactions to an active vaccine without interfering with or preventing daily activity. Grade 2 represents reactogenicity events interfering with daily activities. Grade 3 represents reactogenicity events preventing daily activities.

As previously reported, the 100/15 dose of amezosvatein demonstrated a clinically meaningful and statistically significant improvement for Grade 2 and Grade 3 reactogenicity versus Shingrix. Just 7.3% of participants in the trial receiving the highest dose of amezosvatein (n=55) reported a Grade 2 (interferes with daily activity) or Grade 3 (prevents daily activity) reactogenicity event compared to 33.3% of participants receiving Shingrix (n=225). Amezosvatein's advantage over Shingrix was statistically significant (p<0.001 in a post hoc analysis unadjusted for multiple comparisons) and consistent with local and systemic reactions.

Serious adverse events (SAEs), potentially immune-mediated adverse events (PIMMCs), and medically-attended adverse events (MAAEs) were comparable at Day 421 between amezosvatein (n=166 across all doses studied) and Shingrix (n=225). All amezosvatein SAEs were "not related"; All Shingrix SAEs were "not related" or "unlikely related." Amezosvatein had no PIMMCs reported. Shingrix had one PIMMC reported (polymyalgia rheumatica). All amezosvatein MAAEs were considered "not related" or "unlikely related," except one event of non-shingles bilateral rash. One Shingrix participant reported four MAAEs as part of a constellation of symptoms considered "possibly related" (fatigue, myalgia, headache, migraine), and one additional Shingrix participant had presyncope (near fainting) considered "definitely related," with the investigator noting it was related to study procedure of blood collection. No deaths were reported in the amezosvatein arms. One unrelated death was reported in the Shingrix arm (metastatic sarcoma & venous thrombosis).

Clinical Trial NCT03820414: Safety, Tolerability, and Immunogenicity of CRV-101 in Healthy Adult Subjects. A Phase 1b clinical trial will be conducted at the Family Center for Research with Ubuntu at Tygerberg Academic Hospital, a research center within Stellenbosch University in Cape Town, South Africa, in Q4 2021. Phase 1b study objectives include evaluating the safety, tolerability, and immunogenicity of two intramuscular vaccinations approximately two months apart in HIV-infected children.

In the Phase 1 trial, CRV-101 demonstrated very robust immunogenicity as measured by humoral and cellular responses with no grade 3 injection site side effects and a 1.3% rate of grade 3 systemic side effects ("grade 3" side effects are those vaccination-related reactions severe enough to prevent normal activities).

0 min read
Manufacturer: 
Curevo, Inc
Reviewer: 
Robert Carlson, MD
Vaccine: 
Amezosvatein Shingles Vaccine
VIS: 
PDF
Availability: 
TBD
Generic: 
CRV-101
Drug Class: 
Adjuvanted subunit vaccine
Find Price: 
Discounts
Clinical Trial Phase I: 
Safety, Tolerability, and Immunogenicity of CRV-101 in Healthy Adult Subjects
Clinical Trial Phase II: 
CRV-101 Vaccine for the Prevention of Herpes Zoster in Adults Aged 50 Years and Older
Condition: 
Shingles
Last Reviewed: 
Monday, March 17, 2025 - 11:25
Brand: 
Amezosvatein
Status: 
Candidate
Manufacturer Country ID: 
US
Side Effects: 
Phase 2 study

AADvac1 Alzheimer's Disease Vaccine

AADvac1 Alzheimer's Disease Vaccine

AADvac1 is a therapeutic vaccine candidate for Alzheimer's disease that targets misfolded tau protein, a common denominator of neurofibrillary pathology. The AADvac1 vaccine consists of a synthetic peptide derived from amino acids 294 to 305 of the tau sequence, i.e., KDNIKHVPGGGS, coupled to keyhole limpet hemocyanin; the precise molecular nature of the antigen has not been disclosed. In addition, AADvac1 uses aluminum hydroxide as an adjuvant.

The vaccine candidate showed several unique therapeutic features. It differs from other tau-based research by targeting the formation of pathological tau proteins and the spread of those already formed. AADvac1-induced antibodies discriminate between normal and pathological tau, ensuring only the latter are targeted. In this way, Axon's treatment is more effective and safer, says the company.

In September 2019, Axon Neuroscience published full results after a peer review (Novak et al., 2021). According to their reports, the treatment was safe and well-tolerated. Injection site reactions and transient confusion were the adverse events seen more often in the treated group compared to placebo. 

The Phase II trial ADAMANT study successfully met its primary objective, with AADvac1 shown to be safe and well-tolerated. The exceptional tau antibody response demonstrated by the vaccine is critical when treating the elderly. In addition,  AADvac1 significantly reduced the accumulation of Neurofilament Light Chain, an important biomarker of neurodegeneration, in the blood by 58% (p value=0.004). This was supported by substantially reduced core Alzheimer's disease cerebrospinal fluid biomarkers of tau pathology and tau neurodegeneration, including the most specific CSF biomarker, phosphotau–T217 (p value=0.009).

The company stated, 'AADvac1 is currently the most clinically-advanced tau therapy in development.' For details on AADvac1 clinical studies, see clinicaltrials.gov. AXON Neuroscience is a clinical-stage biotech company founded in 1999 with the world's largest team of researchers focused exclusively on tau-immunotherapies and tau diagnostic platforms.

AADvac1 Vaccine Indication

AADvac1 is indicated as an active immunotherapy vaccine candidate for patients with diagnosed Alzheimer's disease. It instructs the patient's immune system to produce specific antibodies targeting pathological tau. Tau proteins are vital in a brain's healthy, normal functioning. They are involved in various physiological processes, including cell signaling, the dynamics of the cellular cytoskeleton, and protecting DNA. Alzheimer's disease is triggered when these normal tau proteins become pathological by truncation, says the company.

AADvac1 Vaccine Dosage

Patients in the phase 2 study received up to 6 immunization doses.

AADvac1 Alzheimer's Disease Vaccine News

October 29, 2021 - Science Advances published the results of a study examining tau seed accumulation in Alzheimer's disease. The results suggest that from Braak stage III onward, local replication, rather than spreading between brain regions, is the primary process controlling the overall rate of tau accumulation in the neocortical areas. Furthermore, the number of seeds doubles only every five years. Thus, limiting local replication likely constitutes the most promising strategy to control tau accumulation during AD.

June 14, 2021 - Nature Aging published the results of ADAMANT, a 24-month double-blinded, parallel-arm, randomized phase 2 multicenter placebo-controlled trial of AADvac1, an active peptide vaccine designed to target pathological tau in AD.

April 3, 2020 - Vienna-based AXON Neuroscience SE presented the positive results of its Phase II trial for AADvac1, the first tau vaccine to treat and prevent Alzheimer's Disease AAT-AD/PD 2020 conference. AADvac1 exhibited a disease-modifying effect by significantly reducing the neurodegenerative process by 58% in comparison to the placebo arm (p value=0.004) as measured by Neurofilament Light Chain ("NfL") in the blood. NfL released in the blood and cerebrospinal fluid ("CSF") is a dynamic biomarker that reflects the extent of ongoing neurodegeneration in patients with Alzheimer's and other neurological disorders. The Phase II results indicate that AADvac1 prevents further neuronal damage in patients, maintaining levels similar to those typically observed in healthy elderly individuals. The most pronounced effects of the vaccine on clinical outcomes were observed among younger patients. In patients with young onset of Alzheimer's Disease, AADvac1 reduced the clinical decline measured by CDR-SB by 42% in comparison to the placebo arm (p value=0.062), MMSE (reduced by 31%), and ADCS-MCI-ADL (reduced by 26%). 2 Among the subgroup of younger-onset patients, the cognitive and functional effect was consistent with a significantly reduced rate of neuronal NfL accumulation in the blood by 73% in comparison to the placebo arm (p value=0.033), which represents double the effect observed in the study population as a whole.

Furthermore, MRI brain atrophy was considerably reduced in all individual brain areas associated with Alzheimer's Disease. The most substantial decrease of brain volume loss was observed in the cerebral cortex, by 47%, vs. the placebo arm (p value=0.021). This combination of clinical and biomarker outcomes demonstrates the disease-modifying effect of the AADvac1 therapy.

July 17, 2017 - AXON Neuroscience, a leader in tau research, took one further step, completing recruitment for its phase II clinical trial in Alzheimer's Disease. In total, 208 patients with mild AD were enrolled in the 24-month study, powered to evaluate the efficacy and safety of the AADvac1. With top-line data available in mid-2019, the "ADAMANT" phase II study is now the most advanced tau program in Alzheimer's research.

June 5, 2017 - AXON launches a 24-month Phase 1 Pilot Study of AADvac1 in Patients With Non-Fluent Primary Progressive Aphasia.

December 9, 2016 - The Lancet: Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer's disease: a randomized, double-blind, placebo-controlled, phase 1 trial. AADvac1 had a favorable safety profile and excellent immunogenicity in this first-in-man study. However, further tests are needed to corroborate the safety assessment and to establish proof of the clinical efficacy of AADvac1.

AADvac1 Vaccine Clinical Trials

Clinical Trial NCT01850238: Safety Study of AADvac1, a Tau Peptide-KLH-Conjugate Active Vaccine to Treat Alzheimer's Disease (Completed)

AADvac1 is a candidate therapeutic vaccine for Alzheimer's disease that targets misfolded tau protein, a common denominator of neurofibrillary pathology. Based on preclinical results, the intervention is expected to reduce the number of neurofibrillary tangles, remove hyperphosphorylated tau protein, and reduce the oligomerized and insoluble pathological path tau in the brain, to halt the spread of neurofibrillary pathology through the brain, and thus prevent associated cognitive decline.

The vaccine's antigenic determinant is a synthetic peptide derived from a tau protein sequence coupled to keyhole limpet hemocyanin (KLH) and uses aluminum hydroxide (Alhydrogel) as an adjuvant. Presently, AADvac1 is intended as active immunotherapy for patients with diagnosed Alzheimer's disease (AD). Patients will receive 3 - 6 immunization doses; the raised titers of therapeutic antibodies and possible treatment benefits can extend beyond the study's duration. Because of the central role of pathological misfolded tau protein in AD's etiology, the vaccine is expected to be more effective than active or passive immunotherapies aiming to eliminate the amyloid β plaques that have been clinically investigated so far.

Clinical Trial NCT02031198: 18-month Safety Follow-up Study of AADvac1, an Active Tau Vaccine for Alzheimer's Disease (FUNDAMANT) (Completed)

AADvac1 is a candidate therapeutic vaccine for Alzheimer's disease that targets misfolded tau protein, a common denominator of neurofibrillary pathology. Based on preclinical results, the intervention is expected to reduce the number of neurofibrillary tangles, remove hyperphosphorylated tau protein, and reduce the oligomerized and insoluble pathological path tau in the brain, to halt the spread of neurofibrillary pathology through the brain, and thus prevent associated cognitive decline.

The vaccine's antigenic determinant is a synthetic peptide derived from a tau protein sequence coupled to keyhole limpet hemocyanin (KLH) and uses aluminum hydroxide (Alhydrogel) as an adjuvant. Presently, AADvac1 is intended as active immunotherapy for patients with diagnosed Alzheimer's disease (AD). However, according to need, patients will receive additional immunization doses beyond those administered in the preceding phase 1 trial; the raised titers of therapeutic antibodies and possible treatment benefits can extend beyond the study's duration.

Because of the central role of pathological misfolded tau protein in AD's etiology, the vaccine is expected to be more effective than active or passive immunotherapies aiming to eliminate the amyloid β plaques that have been clinically investigated so far.

Clinical Trial NCT02579252: 24 Months Safety and Efficacy Study of AADvac1 in Patients With Mild Alzheimer's Disease (ADAMANT) (Active). 

Alzheimer's disease (AD) is a chronic progressive neurodegenerative brain disorder. Throughout the disease, pathological proteins accumulate in the brain, damaging neurons and causing them to lose connections and die.

Currently, available treatments are designed to compensate for the neurotransmitter loss caused by the disease without affecting the disease process itself.

AADvac1 is designed to raise antibodies against pathological tau protein (the primary constituent of neurofibrillary pathology in AD). These antibodies are expected to prevent tau protein from aggregating, facilitate the removal of tau protein aggregates, and prevent the spreading of pathology, slowing or halting the disease's progress.

0 min read
Manufacturer: 
Axon Neuroscience
Reviewer: 
Robert Carlson, MD
Holly Lutmer PharmD
Vaccine: 
AADvac1 Alzheimer's Disease Vaccine
Generic: 
AADvac1
Clinical Trial: 
https://www.axon-neuroscience.eu/
Drug Class: 
Vaccine
Clinical Trial Phase I: 
Safety Study of AADvac1, a Tau Peptide-KLH-Conjugate Active Vaccine to Treat Alzheimer's Disease
Clinical Trial Phase II: 
24 Months Safety and Efficacy Study of AADvac1 in Patients With Mild Alzheimer's Disease (ADAMANT)
Condition: 
Alzheimer’s Disease
Last Reviewed: 
Tuesday, December 5, 2023 - 17:35
Status: 
Candidate
Manufacturer Country ID: 
SK
Side Effects: 
AADvac1
Ingredients: 
Nature article

Adacel Vaccine 2023

Adacel® Vaccine Description 2023

Sanofi Pasteur Limited Adacel® vaccine (Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis (Tdap) Vaccine, Adsorbed) contains noninfectious tetanus, diphtheria, and pertussis proteins, aluminum phosphate, 2-phenoxyethanol, and residual amounts of formaldehyde and glutaraldehyde. Adacel vaccine does not contain preservatives.

Adacel is a vaccine indicated for active booster immunization against tetanus, diphtheria, and pertussis. Adacel is U.S. Food and Drug Administration (FDA) approved (STN: BL 125111/904 ) for use in persons 10 through 64 years of age and immunization during the third trimester of pregnancy to prevent pertussis in infants younger than two months of age.

The JAMA Pediatrics published an Original Investigation on February 6, 2023: US Infant Pertussis Incidence Trends Before and After Implementation of the Maternal Tetanus, Diphtheria, and Pertussis Vaccine, that concluded following maternal Tdap vaccine introduction, a sustained decrease in pertussis incidence was observed among infants younger than two months, narrowing the incidence gap with infants aged six months to less than 12 months. These findings suggest that maternal Tdap vaccination is associated with a reduction in pertussis burden in the target age group (<2 months) and that further increases in coverage may be related to additional decreases in infant disease.

“Everyone pregnant should feel confident knowing that the Tdap vaccine is safe and effective,” said Linda Eckert, M.D., American College of Obstetricians and Gynecologists’ liaison to the CDC’s Advisory Committee on Immunization Practices in an AAP press release on February 6, 2023. “Knowing that Tdap vaccination during pregnancy protects nine in 10 babies from being hospitalized with whooping cough, I strongly recommend this vaccine to all my pregnant patients for their peace of mind and their family’s health and well-being.”

Adacel Vaccine Indication

Adacel (Tdap) is indicated for active booster immunization to prevent tetanus, diphtheria, and pertussis in people at least ten through 64. Adacel given during the third trimester of pregnancy, helps the pregnant woman create antibodies against the bacteria that cause whooping cough (pertussis) that are passed to her baby before birth. These antibodies help protect the baby against whooping cough during the first few months of life.

Adacel Vaccine Dosage

The Adacel vaccine is administered as an intramuscular injection into the muscle of the upper arm and approved as a single dose in individuals ten through age. 64 Therefore, most people in this age group require only one Tdap shot for protection against these diseases. In addition, Adacel is available in a syringe made without natural rubber latex, which may help reduce risk to patients with an allergy.

Adacel Vaccine News 2019 - 2023

February 6, 2023 - The AAP News published: Study: Tdap vaccination during pregnancy linked to lower pertussis rates in newborns.

January 10, 2023 - The U.S. FDA announced Adacel was approved for immunization during the third trimester of pregnancy to prevent pertussis in infants younger than two months.

January 15, 2019 - 1st Tdap Vaccine Approved for a 2nd Dose.

January 11, 2019 - The U.S. Food and Drug Administration has approved the expanded use of Adacel® (Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis (Tdap) Vaccine Adsorbed) to include repeat vaccination to help protect against tetanus, diphtheria, and pertussis. It is now the first Tdap vaccine in the U.S. approved for a repeat dose in people 10 through 64 years.

Adacel Vaccine Clinical Trials

Adacel has been involved in over 19 clinical studies.

0 min read
Manufacturer: 
Sanofi Pasteur
Reviewer: 
Robert Carlson, MD
Vaccine: 
Adacel Vaccine 2023
VIS: 
PDF
Generic: 
Tdap
Drug Class: 
Vaccine
Find Price: 
Discounts
Clinical Trial Phase I: 
Study of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine (ADACEL®) as a Booster in Adolescents
Clinical Trial Phase III: 
A Study to Evaluate Immunogenicity and Safety of Boostrix Compared to Adacel When Administered as a Booster Vaccination in Adult
Clinical Trial Phase IV: 
A Trial to Evaluate the Safety and Immunogenicity of ADACEL® Vaccine in Persons 65 Years of Age and Older
Condition: 
Pertussis
Last Reviewed: 
Tuesday, February 7, 2023 - 05:20
Brand: 
Adacel
CPT Code: 
90715
Accession Number: 
DB14388
Status: 
Approved
Manufacturer Country ID: 
FR
Side Effects: 
Adverse Reactions
Ingredients: 
Description
Countries: 
US
Europe
UNII: 
N51SPD4A45
Rate Vaccine: 
uh0wUh0i

ACAM2000 Mpox Smallpox Vaccine

ACAM2000® Smallpox Mpox Vaccine Clinical Trials, Dosage, Indication, Side Effects

Emergent BioSolutions' ACAM2000 is a live, cell-cultured, replication-competent vaccinia virus vaccine, administered as a single dose, that protects individuals against mpox and smallpox diseases. ACAM2000 is derived from plaque purification cloning from Dryvax® and calf lymph vaccine, grown in African Green Monkey kidney (Vero) cells, and tested to be free of adventitious agents. The live attenuated vaccine does not contain variola and cannot cause mpox or smallpox. However, the ACAM2000 vaccine includes the vaccinia virus, which belongs to the poxvirus family, genus Orthopoxvirus, that can be transmitted from the vaccine recipient to unvaccinated persons with close contact with the inoculation site or exudate.

ACAM2000, a second-generation smallpox vaccine, replaced Dryvax, a first-generation vaccine derived from calf lymph. Dryvax and ACA2000  vaccines come from the New York City Board of Health strain of vaccinia. Approved by the U.S. FDA on May 2, 2007, ACAM2000 was licensed (STN: BL 125158). The FDA approved the supplemental Biologics License Application to expand the ACAM2000 indication for Mpox on August 29, 2024.

The U.S. Department of Health and Human Services awarded a contract to Emergent in September 2019, valued at approximately $2 billion over ten years, for the continued supply of ACAM2000 into the U.S. Strategic National Stockpile (SNS). The approval and availability of ACAM2000 in the SNS enhance the emergency preparedness of the USA against the use of smallpox as a dangerous biological weapon, says the FDA - Military Medications Guide (NSN): 6505-01-559-0815. On September 21, 2023, the New England Journal of Medicine (NEJM) published a Correspondence that concluded ACAM2000 vaccination prevented mpox disease in Military Personnel.

Emergent announced in August 2024 that it filed an Expression of Interest (EOI) with the World Health Organization (WHO) for the WHO's assessment of the ACAM2000® vaccine to be added as an Emergency Use Listing in connection with the May 2022 mpox outbreak. On May 27, 2022, the WHO published 'Vaccines and Immunization for mpox: Interim Guidance, as did the U.S. Centers for Disease Control and Prevention (CDC), which expanded access via Investigational New Drug Protocol, allowing the use of ACAM2000 for mpox prevention on June 30, 2022. In addition, the WHO and the CDC published updated Annexes to the Vaccines and immunization for Mpox, including ACAM2000.

On April 24, 2025, at the World Vaccine Congress in Washington, D.C., Emergent BioSolutions presented an overview of historical safety data (Prescribing Information and Medication Guide) for ACAM2000®.

Emergent BioSolutions (NYSE: EBS) is a global life sciences company based in Gaithersburg, Maryland. In 2017, Emergent acquired ACAM2000 from Sanofi Pasteur for about $125 million. Emergent BioSolutions confirmed in 2022 that ACAM2000 vaccine deliveries are expected to continue under the terms of the Company's existing contract with the U.S. HHS at unit volume levels ($225-$250) consistent with 2021 deliveries.

ACAM2000 Vaccine Mpox Indication 

U.S. Food and Drug Administration (FDA) approved the supplemental Biologics License Application for the expansion of the indication for ACAM2000® to include Mpox on August 29, 2024, for the prevention of mpox disease in individuals determined to be at high risk for mpox infection. In August 2024, two studies reported that previous smallpox vaccination with ACAM2000 was about 70% protective against mpox clade 2. On June 23, 2023, the U.S. CDC's Advisory Committee on Immunization Practices (ACIP) published updates on the mpox outbreak and vaccine efficacy, as well as a Morbidity and Mortality Weekly Report (MMWR) that presented mpox breakthrough cases in Chicago, IL. On May 18, 2023, the CDC COCA Call confirmed that the Chicago Department of Public Health reported one man vaccinated with ACAM2000 was reinfected with Mpox. A study published on April 25, 2023, found smallpox vaccines given until the mid-1970s offer cross-reactive immunity to mpox, researchers from Karolinska Institutet reported in a study published in the scientific journal Cell Host & Microbe. Public Health France updated on March 23, 2023, confirming that previously vaccinated individuals had been reinfected with Mpox.

ACAM2000 Vaccine Smallpox Indication

ACAM2000 is indicated for active immunization against smallpox disease for persons at high risk for smallpox infection. Smallpox vaccines are no longer routine in the U.S., although some soldiers and laboratory workers still are inoculated. ACAM2000 should not be given to people with Cardiac and Eye disease treated with topical steroids. People eligible for and offered ACAM2000 should be tested for HIV to ensure they are HIV negative, counseled on potential side effects, and given informed consent. The U.S. FDA published Questions about Smallpox and ACAM2000. Please read this Medication Guide before you receive vaccination with ACAM2000. This Guide does not replace consulting with your healthcare provider about ACAM2000 and smallpox disease.

A study published by The Lancet in November 2022 found substantial global spatial heterogeneity in the landscape of smallpox vaccination. Vaccination coverage is estimated to range from 7% to 60% in various countries.

ACAM2000 Vaccination Health Risks

ACAM200 vaccination warnings and precautions include myocarditis, pericarditis, encephalitis, encephalomyelitis, encephalopathy, progressive vaccinia, generalized vaccinia, severe vaccinial skin infections, erythema multiforme major (including Stevens-Johnson Syndrome), eczema vaccinatum resulting in permanent sequelae or death, accidental eye infection (ocular vaccinia), which can cause ocular complications that may lead to blindness, and fetal death. These may occur following primary or revaccination with live vaccinia virus vaccines, including ACAM2000®. These risks are increased in specific individuals and may result in severe disability, permanent neurological sequelae, and/or death.

Myopericarditis following smallpox vaccination is a known health risk for military forces. The incidence of confirmed myocarditis secondary to smallpox vaccination is estimated to be 16.1 per 100,000 service members. A recent U.S. Department of Defense study estimates that myocarditis may impact 12 service members per 100,000. Retrospective studies, which are confirmed by prospective studies, show that more than 10% of patients receiving the smallpox vaccine develop new-onset dyspnoea, chest pain, or palpitations. In addition, myocarditis can range from an influenza-like illness with subtle ECG changes to acute decompensated heart failure and death.

ACAM2000 Vaccine Side Effects

As of August 2024, the FDA labeling for ACAM2000® contains a contraindication for individuals with severe immunodeficiency. Severe localized or systemic infection with vaccinia (progressive vaccinia) may occur in persons with weakened immune systems. Individuals with severe immunodeficiency who are not expected to benefit from the vaccine should not receive ACAM2000®. The risk of experiencing severe vaccination complications must be weighed against the risk of experiencing a potentially severe or fatal smallpox or mpox infection.

A study published on August 26, 2021, concluded that electronic records surveillance of the entire vaccinated military population over ten years found rates of Myopericarditis, defined neurological events, and overall cardiac events consistent with those of prior passive surveillance studies involving Dryvax or ACAM2000 smallpox vaccines. The rate of adjudicated myocarditis among ACAM2000 recipients was 20.06/100,000 and was significantly higher for males (21.8/100,000) and for those < 40 years of age (21.1/100,000). Overall rates for cardiovascular events (Groups 1 and 2 combined) were 113.5/100,000 for the ACAM2000 vaccine. The rate of subjects with one or more defined neurological events was 1.91 (95% CI, 0.71-5.10).

Adverse events following ACAM2000 can be severe, including myopericarditis or Vaccinia virus transmission to household contacts. Additionally, the side effects of the ACAM2000 vaccine, also known as the smallpox vaccine, were discussed in a 2010 publication. Therefore, the vaccination site requires special care to prevent the virus from spreading - Updated Medication Guide. Once vaccinated, the virus remains on the skin's surface for approximately 30 days or until the vaccine site has healed. This means other people can contract the vaccinia virus and get infected. The vaccinia virus is NOT spread by coughing, sneezing, or sexual contact. 

ACAM2000 Vaccine Ingredients 

ACAM2000, developed by Acambis, is a second-generation lyophilized preparation of purified virus (grown in Vero cell line) in HEPES (hydroxyethyl piperazine ethanesulfonic acid)-buffered saline, pH 7.4, containing 1% to 4% human serum albumin USP, 5% mannitol, and trace amounts of antibiotics (100 U/mL polymyxin B and 100 µg/mL neomycin) (John Becher, RPh, CDC, personal communication, 2006). It must be reconstituted before the addition of a diluent.

ACAM2000 Vaccine Dosage

ACAM2000 is administered as a single-dose live virus preparation by the percutaneous route using the multiple puncture technique. ACAM2000 is administered differently from the typical "shot" associated with most vaccinations. A two-pronged stainless steel (or bifurcated) needle is dipped into the vaccine solution, and the skin is pricked several times in the upper arm with a droplet of the vaccine. The virus grows at the injection site, causing a localized infection or "pock" to form. A red, itchy, or sore spot at the vaccination site within 3-4 days indicates that the vaccination was successful, meaning an immune response has occurred. A blister develops at the vaccination site and then dries up, forming a scab that falls off in the third week, leaving a small scar. The vaccine stimulates a person's immune system to develop antibodies and cells in the blood and elsewhere that can help the body fight off an actual smallpox infection if exposure to smallpox ever occurs. Therefore, individuals who receive vaccination with ACAM2000 must take precautions to prevent the spread of the vaccine virus.

ACAM2000 is provided as a lyophilized preparation of purified live virus. After reconstitution, each vial of ACAM2000 vaccine contains approximately 100 doses (0.0025 mL/dose). The concentration of vaccinia virus is 1.0-5.0 × 10^8 plaque-forming units (PFU)/mL or 2.5-12.5 × 10^5 PFU/dose, as determined by plaque assay in Vero cells. In addition, the product contains 2% albumin USP and trace amounts of neomycin sulfate and polymyxin B sulfate.

ACAM2000 Vaccine Breast Milk

Breastfeeding is a contraindication for smallpox vaccination. The U.S. CDC recommends against breastfeeding in women until the risks associated with ACAM2000 vaccine exposure are evaluated. The CDC suggests temporarily withholding breastfeeding in the ten days following vaccination, during which the vaccine content is detectable in Breast Milk.

ACAM2000 Vaccine U.S. Government

The Company announced on September 9, 2025, that a contract modification had been executed for $56 million to supply ACAM2000® to the U.S. government. On November 6, 2024, company revenues from Smallpox Medical Countermeasures (MCM) products increased $108.0 million, or 437%, during Q3 2024, compared to Q3 2023. The increase was primarily due to the timing of USG purchases of ACAM2000® and VIGIV. On September 26, 2024, Emergent announced that it had secured approximately $400 million in orders for 2024 and 2025 associated with its vaccinia product portfolio, including ACAM2000 and CNJ-016. On May 30, 2023, Emergent BioSolutions announced a contract option has been secured to deliver ACAM2000® into the SNS. The option is the third of nine annual contract term extension options. It is valued at approximately $120 million and was awarded for a smaller volume than in prior years under a bilateral modification of the 10-year, roughly $2 billion contract Emergent signed with the Office of the Assistant Secretary for Preparedness and Response (ASPR) in the U.S. Department of Health and Human Services in 2019. The Army Smallpox Vaccinations Program provides insights into Package Inserts, Medication Guides, the DHA Trifold Brochure, Household contact information, and frequently asked questions and answers.

ACAM2000 Vaccine CPT Codes

The AMA-issued CPT code (90622) describes the ACAM2000 vaccine, manufactured by Sanofi Pasteur Biologics Co., for active immunization against smallpox disease in persons at high risk for smallpox infection. 

ACAM2000 Vaccine News

September 9, 2025 - The Company projected sales for ACAM2000® vaccine and ancillary products to exceed $120 million this year, driven by a diverse base of customers.

August 29, 2024 - "The FDA approval of ACAM2000® for immunization against mpox in high-risk individuals further strengthens and broadens our industry-leading smallpox portfolio, which includes VIGIV® and TEMBEXA®, said Joe Papa, president and CEO of Emergent.

August 19, 2024 - 50,000 doses of ACAM2000® will be donated to Direct Relief for potential deployment in Africa.

May 30, 2023 - "This option represents the importance the U.S. government places in preparing for the threat of smallpox," said Paul Williams, SVP and Products Business Head, Emergent BioSolutions. "It also highlights the value placed by the U.S. government in maintaining domestic manufacturing capabilities and the important role of public-private partnerships in addressing known and unknown public health threats."

September 14, 2022 - The U.S. CDC Research Letter - Volume 28, Number 11—November 2022: Mpox in Patient Immunized with ACAM2000 Smallpox Vaccine During 2022 Outbreak. We report a case of Mpox in the United States in a patient vaccinated with the ACAM2000 smallpox vaccine eight years earlier. Despite his vaccination status, he still contracted the disease. In addition, he showed prodromal symptoms preceding the development of painless penile lesions that later merged.'

June 30, 2022 - The U.S. CDC published 'Considerations for Mpox Vaccination: What You Need to Know.

September 3, 2019 - Emergent BioSolutions Awarded 10-Year HHS Contract to Deliver ACAM2000 Into the Strategic National Stockpile. Robert G. Kramer Sr., president and chief executive officer of Emergent BioSolutions, stated, "Emergent applauds the U.S. government's continued focus on national security demonstrated through its long-term stockpiling strategy, which ensures a sustainable supply of critical medical countermeasures such as ACAM2000 vaccine, and its investment in a stable domestic manufacturing infrastructure to help protect the U.S. population against smallpox in the event of an attack." 

June 21, 2019 - Emergent BioSolutions completes acquisition of ACAM2000® Business from Sanofi.

August 24, 2015 - U.S. FDA Risk Evaluation and Mitigation Strategy Release Letter - ACAM2000 - BLA 125158/58.

March 20, 2015 - PLOS One published - A peer-reviewed Prospective Study of the Incidence of Myocarditis/Pericarditis and New Onset Cardiac Symptoms following Smallpox Vaccination. Conclusions - Passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical, transient cardiac muscle injury post-vaccinia immunization, with a rate 60 times higher than the incidence rate of overt clinical cases, requires further study to include long-term outcomes surveillance.

July 9, 2013 - Unintentional transfer of vaccinia virus associated with smallpox vaccines: ACAM2000 compared with Dryvax.

May 25, 20110 - ACAM2000™: The new smallpox vaccine for the United States Strategic National Stockpile.

April 17, 2008 - ACAM2000 is a newly licensed cell culture-based live vaccinia smallpox vaccine. Studies with ACAM2000 indicate that it closely matches the safety of Dryvax in both non-clinical and clinical trials. ACAM2000 met two of the four primary surrogate efficacy endpoint criteria for the Phase III clinical trials. Concerns exist regarding the incidence of Myopericarditis Associated with ACAM2000 and Dryvax. However, so far, the cardiac events seem to be self-limited.

ACAM2000 Clinical Trials

ACAM2000 Smallpox vaccine has been involved in various clinical trials.

0 min read
Manufacturer: 
Emergent BioSolutions
Reviewer: 
Robert Carlson, MD
Vaccine: 
ACAM2000 Mpox Smallpox Vaccine
VIS: 
PDF
Availability: 
Government Supplied
Drug Class: 
Live attenuated vaccine
Find Price: 
Discounts
Clinical Trial Phase II: 
Dose Study of ACAM2000 Smallpox Vaccine in Previously Vaccinated Adults
Clinical Trial Phase III: 
VA-006 Vaccinia Vaccine (ACAM2000) for the Production of VIGIV
Clinical Trial Phase IV: 
VA-008 ACAM2000® Vaccination of Plasma Donors for the Production of VIGIV
Lab Test: 
CDC
Condition: 
Smallpox
Last Reviewed: 
Friday, September 12, 2025 - 06:30
Brand: 
ACAM2000
CPT Code: 
90622
Accession Number: 
DB14711
Status: 
Approved
Manufacturer Country ID: 
US
FDA First In Class: 
Yes
Side Effects: 
Emergent
Ingredients: 
Ingredients
Countries: 
USA
Australia
U.K.
UNII: 
4SV59689SK
Cell Line Design & Development: 
African Green Monkey kidney (Vero) cells
Rate Vaccine: 
okXJPSXS
Location tags: 
United States of America
Europe

Hecolin Hepatitis E Vaccine

Hecolin Hepatitis E Vaccine

Hecolin is a recombinant protein-subunit hepatitis E vaccine (HEV239) that contains the hepatitis E virus (HEV)-like particles prepared using a recombinant Escherichia coli expression system. Since 2011, the vaccine has been approved for use in China in people aged 16 and above and is recommended for individuals at high risk of HEV infection. Hecolin® was found well tolerated and has been demonstrated to be safe for adults. In 2015, the World Health Organization (WHO) recommended using Hecolin in disease outbreak settings.

The vaccine protects against symptomatic HEV infection with a very high efficacy rate. Data on this protection primarily applies to genotype 4 diseases; data on diseases caused by other genotypes are either too limited (genotype 1) or unavailable (genotype 2 and 3). The vaccine can effectively lower, but not eliminate, the risk of asymptomatic infection. The duration of follow-up in the available published reports has been up to nearly 2 years; some unpublished data for up to 4 years after completing immunization are available. Long-term efficacy beyond this time point, duration of protection, and the need and timing for booster dose remain to be determined.

On January 8, 2025, a phase 3 case-control clinical study conducted during an HEV outbreak in Bentiu (South Sudan) estimated the effectiveness of a two-dose regimen against HEV genotype 1 during a protracted outbreak, supporting its use in similar contexts. These findings indicate moderate to high two-dose vaccine effectiveness using several study designs and analytical methods.

Hecolin® was developed and manufactured by Xiamen Innovax Biotech Co., Ltd. in Xiamen, China.

Hecolin Hepatitis E Vaccine Indication

Hecolin is a vaccine that is indicated to prevent hepatitis E. In March 2024, the WHO strongly recommended that in specific settings, women of childbearing age, including those who are pregnant, should have access to Hecolin accompanied by relevant information on its benefit-risk profile. However, there is no data on its protection against severe forms of the disease, such as acute liver failure, which is particularly frequent in pregnant women. A study by Wasuwanich et al. in 2021 focused on hepatitis E-related hospitalizations in the United States between 2010 and 2017, noting an increase in hospitalization rates over that period.

Hecolin Hepatitis E Vaccine Dosage

Hecolin is administered intramuscularly into the deltoid muscle as a single injection on Days 1, 29, and 180. 

Hecolin Stockpile

Since 2015, the World Health Organization has recommended its use in outbreak settings. The WHO’s International Coordinating Group on Vaccine Provision maintains a stockpile of hepatitis E vaccines for emergencies. In the United States, hepatitis E is relatively underexplored, and vaccine development for this disease has not been a priority.

Hecolin Hepatitis E Vaccine News

January 14, 2025 - Iza Ciglenecki, Operational research coordinator at MSF Switzerland, stated, ‘‘Our study then compared the vaccination status of 201 patients testing positive for hepatitis E between May and December 2022 with those in their neighborhood presenting no symptoms. Despite fewer hepatitis E cases than expected after vaccination, our study revealed that two doses of vaccine were effective, an excellent result given the particular context of a camp for displaced people.’’

January 10, 2025 - A study published by The Lancet stated that the results of this study, combined with the existing evidence from clinical trials, suggest that a two-dose regimen of the Hecolin vaccine could be an effective and feasible strategy for controlling hepatitis E outbreaks. 

July 17, 2024 - The Lancet: Volume 12, Issue 11 - Hepatitis E vaccination: continued benefit for pregnant women in vulnerable settings.

July 26, 2019 - Human HEV includes four genotypes; the nonepidemic, zoonotic genotypes (typically 3 and 4) have gained increasing recognition in North America and Europe over the past decade because of the potential risk of transmission through food, blood transfusions, and organ donation. However, relatively little attention and few resources have been invested into genotypes 1 and 2 (g1/g2), which cause outbreaks among the world’s most vulnerable populations living or access to safe water and sanitation infrastructure. 

May 2, 2019—On May 1, the first U.S. participants in the clinical trial of Hecolin were vaccinated. This is the first time the FDA has approved a Chinese vaccine for a clinical trial in the U.S. The trial will be carried out in three phases. Phase 1 is scheduled to enroll 25 U.S. volunteers, and Phases 2 and 3 are FDA-approved vaccine trials expected to be conducted in a third country.

Hecolin Hepatitis E Vaccine Clinical Trial

Clinical Trial NCT03827395: Safety Study of Hepatitis E Vaccine (HEV239) in Healthy U.S. Adult Population. This is a Phase I double-blind, randomized, placebo-controlled trial (1:4 ratio of placebo to vaccine) of Hepatitis E virus vaccine containing a 239 amino acid subfragment of Hecolin(R) (HEV-239) in 25 U.S. males and non-pregnant females ages 18 - 45 (inclusive) to assess the safety, reactogenicity, and immunogenicity of Hecolin  (HEV-239).

The main adverse events associated with its use have been local reactions at the injection site. Current evidence demonstrates that this vaccine is highly immunogenic, with nearly all the recipients seroconverting after three doses administered in a 0, 1, and 6-month schedule. Limited data show that even two doses (at 0 and 6 months, or 0 and 1 month) lead to a high rate of seroconversion through the antibody titers are lower.

0 min read
Manufacturer: 
Innovax
Reviewer: 
Robert Carlson, MD
Vaccine: 
Hecolin Hepatitis E Vaccine
VIS: 
PDF
Availability: 
China
Generic: 
HEV239
Drug Class: 
Recombinant vaccine
Clinical Trial Phase I: 
Safety Study of Hepatitis E Vaccine (HEV239) in Healthy US Adult Population
Clinical Trial Phase II: 
Hepatitis E vaccination: continued benefit for pregnant women in vulnerable settings
Clinical Trial Phase III: 
The effectiveness of two doses of recombinant hepatitis E vaccine in response to an outbreak in Bentiu, South Sudan: a case–cont
Clinical Trial Phase IV: 
Phase Ⅳ Clinical Trial of Recombinant Hepatitis E Vaccine
Lab Test: 
CDC
Condition: 
Hepatitis E
Last Reviewed: 
Saturday, January 25, 2025 - 07:00
Brand: 
Hecolin
Status: 
Approved
Manufacturer Country ID: 
CN
FDA First In Class: 
Yes
Countries: 
China
Pakistan

MV-CHIK Chikungunya Vaccine

MV-CHIK Vaccine Candidate Clinical Trials, Dosage, Indication, Side Effects

MV-CHIK is a vaccine candidate utilizing Themis’ measles vector platform. MV-CHIK consists of a recombinant live Schwarz-strain measles-vectored vaccine expressing chikungunya virus structural proteins. Upon vaccination with MV-CHIK, the measles virus delivers the CHIKV antigens directly to antigen-presenting cells susceptible to the measles virus, including dendritic cells and monocytes. This allows for the mounting of CHIKV-specific cellular and humoral immune responses without the need for an additional adjuvant (Brandler et al., 2013MV-CHIK-induced ed neutralizing antibodies are cross-protective against all circulating CHIKV lineages, as demonstrated with serum from immunized NHPs and serum pools from human clinical trial participants (Rossi et al. 2019). In addition to immune responses against chikungunya virus structural proteins, the recombinant vaccine significantly increased measles-specific IgG titers at both doses evaluated. This indicates that the measles backbone of MV-CHIK elicits an immune response. This enhanced immunity against measles could be a major benefit of MV-CHIK.

Research data from October 13, 2023, show that the MV-CHIK vector vaccine induced a functional transgene-specific CD4+ T cell response. This, together with the evidence of neutralizing antibodies as a correlate of protection for CHIKV, makes MV-CHIK a promising vaccine candidate.

Themis’ vaccination vector can incorporate large recombinant genes to code for selected antigens into its genome. 

MV-CHIK Indication

MV-CHIK is indicated to prevent Chikungunya disease.

MV-CHIK Dosage

In the Phase 2 clinical trial, MV-CHIK was administered as two intramuscular injections.

MV-CHIK Clinical Trials

Clinical Trial NCT03807843: Chikungunya Vaccine Study in Previously Exposed Adults.

Clinical Trial NCT02861586: Phase II Study to Evaluate Safety and Immunogenicity of a Chikungunya Vaccine (MV-CHIK-202).

0 min read
Manufacturer: 
Themis Bio
Reviewer: 
Robert Carlson, MD
Vaccine: 
MV-CHIK Chikungunya Vaccine
Generic: 
MV-CHIK
Drug Class: 
Live recombinant measles vector-based vaccine
Clinical Trial Phase II: 
Safety, Tolerability and Long-term Immunogenicity of Different Formulations of a Chikungunya Vaccine (V184-005)
Condition: 
Chikungunya
Last Reviewed: 
Wednesday, June 26, 2024 - 06:20
Status: 
Candidate

mRNA-1893 Zika Vaccine

mRNA-1893 Zika Vaccine

Moderna's mRNA-1893 vaccine candidate contains an mRNA sequence encoding for the structural proteins of the Zika virus. It is designed to cause cells to secrete virus-like particles, mimicking the cell's response after a natural infection. Preclinical data published in the Journal of Infectious Diseases have shown that vaccination with mRNA-1893 protected mice against Zika virus transmission during pregnancy.

On August 19, 2019, Moderna, Inc. announced that the U.S. Food and Drug Administration (FDA) had granted Fast Track Designation for its investigational mRNA-189. It is currently being evaluated in a Phase 1 study to prevent Zika virus infection in healthy adults. This project has been funded in whole or in part with Federal funds from the Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority (BARDA), under Contract No. HHSO100201600029C.

As of July 12, 2022, the phase 1 study (mRNA-1893-P201) is active in Puerto Rico, with a completion date scheduled for April 26, 2024. On August 3, 2022, Moderna confirmed that the mRNA-1893 Phase 2 study was ongoing.

The Lancet Infectious Disease published on January 19, 2023: Promising efforts to develop an mRNA vaccine against Zika. These findings support the continued development of mRNA-1893 against the Zika virus, which was well tolerated at all evaluated dose levels and induced strong Zika virus-specific serum nAb responses after two doses, regardless of baseline flavivirus serostatus. On April 20, 2023, the journal NPJ Vaccines published - The first-generation ZIKV mRNA vaccine, mRNA-1325, was initially generated, and as additional strain sequences became available, a second mRNA vaccine, mRNA-1893, was developed. Herein, we compared the immune responses following mRNA-1325 and mRNA-1893 vaccination and reported that mRNA-1893 generated comparable neutralizing antibody titers to mRNA-1325 at 1/20th of the dose and provided complete protection from ZIKV challenge in non-human primates. In-depth characterization of these vaccines indicated that the observed immunologic differences could be attributed to a single amino acid residue difference that compromised mRNA-1325 virus-like particle formation. These findings support the continued development of mRNA-1893 against Zika virus.

Headquartered in Cambridge, Mass., Moderna (Nasdaq: MRNA) currently has strategic alliances for development programs.

mRNA Technology

Recognizing the broad potential of mRNA science, Moderna set out to create an mRNA technology platform that functions very much like an operating system on a computer. It is designed to plug and play interchangeably with different programs. Generally, the only thing that changes from one potential mRNA medicine to another is the coding region – the actual genetic code that instructs ribosomes to make protein. Utilizing these instruction sets gives the investigational mRNA medicines a software-like quality. Moderna also can combine different mRNA sequences encoding for various proteins in a single mRNA investigational medicine.

mRNA-1893 Vaccine Indication

Zika virus is the first and only flaviviral disease the WHO (2016) declared a public health emergency because of devastating congenital disabilities following maternal infection. mRNA-1893 is indicated for avoiding transmission of the Zika disease from a mother to an unborn child.

mRNA-1893 Vaccine Dosage

Interim Phase 1 Data - All four cohorts (10 µg, 30 µg, 100 µg, 250 µg) of the Phase 1 study of mRNA-1893 have been dosed. An interim study analysis reports safety and immunogenicity data from the ten µg and 30 µg cohorts. In addition, neutralizing antibody titers were assessed using the Plaque Reduction Neutralization Test (PRNT50) and microneutralization assays (M.N.), which provide equivalent guidance for interpreting the neutralizing immune response.

mRNA-1893 Vaccine News

May 4, 2022 - Moderna confirmed the Phase 2 study of mRNA-1893 is ongoing in the U.S. and Puerto Rico and is being developed in collaboration with BARDA.

November 10, 2021 - The Hindustan Times reported that ZIKA virus cases had reached over 100 cases. Of the 105 positive cases, 17 are now negative.

November 4, 2021 - Moderna announced that its phase 2 study of mRNA-1893 is ongoing in the U.S. and Puerto Rico. mRNA-1893 is being developed in collaboration with BARDA. 

April 14, 2020 - The first interim analysis of the Phase 1 study shows that ten µg and 30 µg dose levels seroconverted 94% and 100% of seronegative participants, respectively, and effectively boosted seropositive participants; both dose levels were generally well-tolerated.

August 19, 2019 - Moderna Inc. announced that the Food and Drug Administration had approved its potential vaccine for the Zika virus for a fast track to approval. Fast Track is designed to facilitate the development and expedite the review of therapies and vaccines for serious conditions and to fill an unmet medical need. In addition, programs with Fast Track designation may benefit from early and frequent communication with the FD and a rolling marketing application submission. 

mRNA-1893 Vaccine Clinical Trials

mRNA-1893 Zika vaccine is currently being studied in two clinical trials. These were descriptive studies, with no formal hypothesis testing in either trial. Both trials are registered with ClinicalTrials.gov, NCT03014089 (mRNA-1325 trial) and NCT04064905 (mRNA-1893 trial).

Findings: The mRNA-1325 trial was done from Dec 14, 2016, to Aug 16, 2018. Ninety participants were enrolled: 53 (59%) participants were women, and 37 (41%) were men, 84 (93%) were White, and 74 (82%) were not Hispanic or Latino. All three dose levels of mRNA-1325 (10, 25, and 100 μg) were generally well tolerated, but the vaccine elicited poor Zika virus-specific nAb responses. At 28 days after dose two, geometric mean titres (GMTs) were highest for mRNA-1325 10 μg (10·3 [95% CI 5·9–18·2]). The mRNA-1893 trial was done from July 23, 2019, to March 22, 2021. One hundred twenty participants (70 [58%] women and 50 [42%] men) were enrolled, most participants were White (89 [74%]) and not Hispanic or Latino (91 [76%]). In the mRNA-1893 trial, solicited adverse reactions in participants who received a vaccine were mainly grade 1 or 2 and occurred more frequently at higher dose levels and after dose two. No participants withdrew due to an unsolicited treatment-emergent adverse event, and most of these events were not treatment-related. On day 57, all evaluated mRNA-1893 dose levels induced robust Zika virus-specific nAb responses, independent of flavivirus serostatus, that persisted until month 13. At day 57 in participants who were flavivirus seronegative, plaque reduction neutralization titre test nAb GMTs were highest for mRNA-1893 100 μg (454·2 [330·0–619·6]); in participants who were flavivirus seropositive, GMTs were highest for mRNA-1893 10 μg (224·1 [43·5–1153·5]) and mRNA-1893 100 μg (190·5 [19·2–1887·2]).

0 min read
Manufacturer: 
Modernatx
Reviewer: 
Robert Carlson, MD
Holly Lutmer PharmD
Vaccine: 
mRNA-1893 Zika Vaccine
Generic: 
mRNA-1893
Clinical Trial: 
https://trials.modernatx.com/
Drug Class: 
mRNA Vaccine
Clinical Trial Phase I: 
Safety, Tolerability, and Immunogenicity of Zika Vaccine mRNA-1893 in Healthy Flavivirus Seropositive and Seronegative Adults
Clinical Trial Phase II: 
A Study of Zika Vaccine mRNA-1893 in Adult Participants Living in Endemic and Non-Endemic Flavivirus Areas
Condition: 
Zika
Last Reviewed: 
Thursday, January 4, 2024 - 06:10
Status: 
Candidate
Manufacturer Country ID: 
US