Search API

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).

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.

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]).

NanoVax Herpes Simplex Virus Vaccine Description 2022

NanoVax is an adjuvant platform used in the development of a vaccine candidate that will provide protection against the two viruses that can cause genital herpes. The subunit vaccine composition comprises isolated surface glycoproteins from herpes simplex viruses, fusion proteins, or fragments mixed in varied combinations with a nanoemulsion, which is a potent immune enhancer.

NanoVax Indication

This vaccine candidate will provide protection against HSV1 and HSV2, two viruses that cause genital herpes.

NanoVax Dosage

NanoVax is administered intranasally.  

Intranasal NanoVax platform elicits both mucosal and systemic immunity through its novel oil-in-water nanoemulsion (NE) adjuvant, offering a unique advantage to combat sexually transmitted infections (STIs) including genital herpes.

The mucosal immunity elicited by intranasal NE vaccines provides critical protection against infections at the port of entry by which a pathogen enters the body.

The intranasal NanoVax HSV vaccine has demonstrated safety and efficacy in both prophylactic and therapeutic animal models for genital herpes.

In a prophylactic guinea pig study, the intranasal vaccine prevented genital herpes infection in 92 percent of animals vaccinated.

Therapeutic study animals previously infected with genital herpes who received the BlueWillow NanoVax vaccine reduced recurrent lesions and viral shedding by more than 50 percent compared to animals who received no treatment.

NanoVax News 2018 - 2022

September 21, 2021 - Announced the formation of the Company’s Scientific Advisory Board (SAB) with three leading viral infectious disease experts. The SAB will provide strategic and scientific counsel to BlueWillow’s clinical programs. Robin Isaacs, M.D., Akiko Iwasaki, Ph.D. and Steve Projan, Ph.D. are newly named members of the SAB.

July 23, 2019 - Announced the issuance of U.S. patent number 10,206,996 to BlueWillow for the development of an intranasal NanoVax® herpes simplex virus (HSV) vaccine. The patent protects the use of BlueWillow’s unique NanoVax adjuvant platform in the development of a vaccine that provides protection against HSV-1 and HSV-2, the two viruses that can cause genital herpes.

May 7, 2018 - NanoBio Corporation, a clinical-stage biopharmaceutical company, announced that it has changed its corporate name to BlueWillow Biologics® in conjunction with the closing of a $10 million Series A financing. The Series A financing round was led by North Coast Technology Investors, Line Moon Ventures and the University of Michigan through its MINTS initiative.

Recent research conducted by the University of Cincinnati in conjunction with BlueWillow has demonstrated that an intranasal NE vaccine elicits protection in both the prophylactic & therapeutic guinea pig models for HSV-2.