Dengvaxia® Vaccine Clinical Trials, Dosage, Efficacy, Lab Test, Side Effects
Sanofi Pasteur's Dengvaxia® (CYD-TDV) is a live attenuated tetravalent chimeric vaccine made using recombinant DNA technology by replacing the PrM (pre-membrane) and E (envelope) structural genes of yellow fever attenuated 17D strain vaccine with those from the four dengue serotypes. Dengvaxia is U.S. Food and Drug Administration (FDA)-approved (Clinical Reviewer: Ralph LeBlanc, STN 125682.0) and indicated for preventing dengue virus serotypes 1, 2, 3, and 4. In 2015, Sanofi Pasteur introduced the first dengue vaccine in endemic countries. Sanofi announced in 2017 that people who received Dengvaxia and have not been previously infected with one of the dengue viruses might be at risk of developing severe dengue if they get dengue after vaccination. Dengvaxia is not approved for use in individuals whose immunization information is unknown.
On May 1, 2019, Dengvaxia was approved (STN: 125682) by the U.S. FDA for use in children 9-16 years old living in an area where dengue is common (such as the U.S. territories of American Samoa, Puerto Rico, and U.S. Virgin Islands), with laboratory-confirmed prior dengue virus infection. On January 22, 2020, the FDA approved the request submitted by Sanofi Pasteur Inc. on July 23, 2019, to supplement the Dengvaxia Biologics License Application. In addition, the FDA confirmed on July 3, 2023, that the Approval Letter for BL 125682/40 was approved on June 30, 2023, and reissued on August 8, 2023, approved for use in individuals 6 through 16 years of age with laboratory-confirmed previous dengue infection and living in endemic areas. The review of this FDA supplement was associated with the following National Clinical Trial numbers: NCT01373281, NCT01374516, NCT00842530, and NCT01983553.
The World Health Organization (WHO) stated that following the release of the long-term safety data stratified by serostatus on November 29, 2017, a Strategic Advisory Group of Experts on Immunization (SAGE) working group on dengue vaccines concluded that for countries considering vaccination as part of their dengue control program, a "pre-vaccination screening strategy" would be the preferred option, in which only dengue-seropositive persons are vaccinated.
The Lancet Infectious Diseases journal published results from a prospective, longitudinal, population-based cohort study on March 22, 2024. These researchers reported that a single dose of Dengvaxia (CYD-TDV) did not confer protection against virologically confirmed dengue in children with none or one previous DENV infection at baseline. This study's Interpretation is that the risk of developing virologically confirmed dengue after a single dose of CYD-TDV varied by baseline DENV serostatus. In a related Editorial, the authors wrote, 'The findings of Ylade and colleagues emphasize the need to acquire DENV baseline status before rolling out this type of vaccine.'
Dengvaxia - NDC CODE: 49281-605; UNII 75KB2HPX5H; U.S. License No. 1725; EMA: EMEA/H/C/004171
Sanofi Pasteur Inc. (SNY) is the manufacturer of the Dengvaxia vaccine. Sanofi U.S. Headquarters at 55 Corporate Drive, Bridgewater, NJ 08807. And DBA: P.T. Sanofi-Aventis Indonesia.
Denvaxia Vaccine Availability
Dengvaxia is no longer available in the United States, except in Puerto Rico, where it will be available to select children in 2025. In January 2024, Sanofi-Pasteur announced it would cease manufacturing Dengvaxia for children, citing a lack of demand in the global market as the reason for discontinuing production of this vaccine. On June 26, 2024, the U.S. CDC's vaccine committee reviewed two presentations led by Nicholas Bergren, PhD, MBA, and Joshua Wong, MD. Dengvaxia remains a WHO Prequalified Listed vaccine in 2024.
Dengvaxia Pre-Vaccination Test
The U.S. CDC states that proof of a previous dengue infection is required to administer the Dengvaxia vaccine to children and adolescents. Any test used for screening must meet the minimum test performance standards for its results to be considered reliable: sensitivity≥75%, specificity≥98%.
Dengvaxia Vaccine Efficacy
The journal Vaccine published an article on August 22, 2023, concluding that Dengvaxia's efficacy was 56.5 % (95 % CI, 43·8–66·4) and 60.8 % (95 % CI, 52.0–68.0) against symptomatic, virologically confirmed dengue caused by any serotype more than 28 days after the third dose in Asia (2 to 14-year children) [14] and Latin America (9 to 16-year children).
Dengvaxia Vaccine Price
According to the U.S. CDC, Vaccine for Children for the uninsured through immunization programs costs $95.93 per dose, while the commercial pricing for the Dengvaxia® vaccine is $100.98. Dengvaxia® vaccine is sold in pharmacies in Costa Rica for approximately $130. Additional vaccine price and discount information is posted at InstantRx™. In addition, a study published in 2021 focused on the cost-effectiveness of dengue vaccination in Puerto Rico, which found an incremental cost-effectiveness ratio of USD 122,000 per QALY gained per vaccination.
Dengvaxia Vaccine Indication
Dengvaxia is recommended for routine use by the U.S. CDC's Advisory Committee on Immunization Practices (ACIP). On October 20, 2022, the ACIP meeting reviewed a vaccine presentation and Dengue Epidemiology. On June 24, 2021, the U.S. CDC's Dengue Vaccine Workgroup reviewed the following presentations: Overview; Dengue Vaccine Knowledge and Attitudes in Puerto Rico; Implementation of Dengue Vaccine in Puerto Rico; Dengue Vaccine Evidence to Recommendations Framework; and VFC Resolution Update. In addition, the CDC confirmed on December 17, 2021 - Recommendations of the Advisory Committee on Immunization Practices, U.S. On October 26, 203, Dr. Wilbor Chen's workgroup confirmed about 100 pediatric doses of Dengvaxia had been administered in Puerto Rico. The CDC says Dengvaxia is not approved for use in U.S. travelers who are visiting but not living in an area where dengue is common.
The CDC reported a model predicts that in a moderate transmission scenario (San Juan, PR) with a previous dengue prevalence of 50% in the eligible age group for vaccination, using a serologic screening test with 80% sensitivity and 95% specificity over ten years (vaccinating children aged nine years with 80% of children aged nine years screened), 3,415 hospitalizations would be prevented and an additional 184 hospitalizations would occur; that translates to averting 19 hospitalizations for every further vaccine-associated hospitalization.
Dengvaxia Vaccine Immunocompromised Individuals
Do not administer DENGVAXIA to individuals with severe immunodeficiency or immunosuppression due to disease or therapy.
Dengvaxia Vaccine Pregnancy and Breastfeeding
There have been no specific studies of DENGVAXIA performed among pregnant women. According to the CDC, the increased risk for dengue-related complications in pregnant females has not been explicitly studied in the Dengvaxia trial; the limited number of pregnant females inadvertently vaccinated during the trial had a similar frequency of adverse pregnancy outcomes (e.g., spontaneous abortion, intrauterine death, and stillbirth) as occurred in the control group. However, the number of vaccinated pregnant females was insufficient to determine the possible effect of Dengvaxia on pregnancy.
Data are not available to evaluate the safety of Dengvaxia in breastfeeding infants. Therefore, the developmental and health benefits of breastfeeding should be considered in conjunction with the risk for DENV infection in the mother and infant.
Dengvaxia Vaccine Dosage
The U.S. CDC's ACIP recommended in June 2021 that 3-doses of Dengvaxia be administered six months apart at months 0, 6, and 12 in persons 9-16 years of age with laboratory-confirmed previous dengue virus infection and living in areas where dengue is endemic (common). However, the CDC published updated vaccination schedules for 2022, which do not indicate any Dengvaxia coadministration advisories. On March 29, 2022, the peer-reviewed journal The Lancet reported that a 'CYD-TDV booster one year or two years after the two-dose or three-dose primary vaccination regimen does not elicit a consistent, meaningful, meaningful booster effect against all dengue serotypes in participants who are seropositive for dengue at baseline.'
Dengvaxia Vaccine Limitations
Dengvaxia is a prophylactic, tetravalent, live-attenuated, chimeric viral vaccine built on a yellow fever 17D backbone. Limitations of use: DENGVAXIA is not approved for use in individuals not previously infected by any dengue virus serotype or for whom this information is unknown. Those not previously infected are at increased risk for severe dengue disease when vaccinated and subsequently infected with the dengue virus. In addition, when an individual is infected with one dengue serotype, subsequent infection with another may result in more intense conditions. For example, researchers from Duke-NUS Medical School reported that the dengue virus serotype 2 (DENV2) changes its shape through Envelope protein mutations to evade vaccines and therapeutics.
Patients must receive a lab test showing a past infection with dengue before receiving the vaccine. Dengvaxia is not for use in individuals not previously infected by any dengue virus serotype or for whom this information is unknown. Before being vaccinated with Dengvaxia, the CDC vaccine committee informs healthcare providers if a patient has dengue symptoms or lives in or has recently traveled to an area with a risk of dengue and has not previously been infected, they are at increased risk for Severe Dengue disease when vaccinated and subsequently infected with the dengue virus.
From the first administered dose up to month 72, 53 deaths (0.2%) for subjects who received DENGVAXIA and 34 deaths (0.3 %) for subjects who received placebo were reported in 9 of the 12 studies conducted among subjects six through 16 years of age with at least six months follow-up. None of the deaths were considered related to vaccination. Causes of death among subjects were consistent with those generally reported in children and adolescent populations.
Gabriela Paz Bailey, M.D., Ph.D., MSc Dengue Branch, Division of Vector-Borne Diseases, presented the Dengue Vaccine Evidence to Recommendations Framework on June 24, 2021.
Dengvaxia Vaccine Side Effects
Dengvaxia increases the risk of severe dengue in those who experience their first natural infection after vaccination. The most significant adverse event is hospitalization or severe dengue after vaccinating a seronegative person misclassified as a seropositive. Therefore, healthcare professionals must evaluate individuals for prior dengue infection to avoid vaccinating individuals who have not previously been infected with the dengue virus. The most commonly reported side effects of Dengvaxia were headaches, muscle pain, joint pain, fatigue, injection site pain, and low-grade fever. Update CDC precautions included Pregnancy, HIV infection without evidence of severe immunosuppression, and Moderate or severe acute illness with or without fever. Contraindications include severe immunodeficiency (e.g., hematologic and solid tumors, receipt of chemotherapy, congenital immunodeficiency, long-term immunosuppressive therapy, or patients with HIV infection who are severely immunocompromised). The safety and efficacy of Dengvaxia have not been assessed in persons with HIV infection. However, ongoing clinical studies estimate the vaccine's use in adults with well-controlled HIV infection.
Dengvaxia Tests
On May 5, 2022, Anitoa Systems announced the availability of an RT-PCR solution for testing the dengue virus. The multiplex test detects several target genes in a sample, which researchers show highly expressed in patients who later develop severe symptoms. In addition, the peer-reviewed journal The Lancet published on May 4, 2022 - Accuracy and efficacy of pre-dengue vaccination screening for previous dengue infection with a new dengue rapid diagnostic test: a retrospective analysis of phase 3 efficacy trials. The OnSite IgG RDT should provide a valuable tool for screening for previous dengue infection at the point of vaccination.
On February 3, 2022, EUROIMMUN announced that its EUROIMMUN® Anti-Dengue Virus NS1 Type 1-4 ELISA (IgG) was cited by the U.S. CDC as part of the two-step testing algorithm guidance for pre-vaccination screening for the Dengvaxia vaccine that is used to prevent future dengue disease. On May 2, 2022, The Lancet published a retrospective analysis of Phase 3 efficacy trials, concluding that the OnSite IgG RDT test should provide a valuable tool for screening for previous dengue infection at the point of vaccination.
Dengvaxia Vaccine Legal Issues
The Philippines' Public Attorney's Office (PAO) has filed seven more civil cases for the families of those who died after reportedly getting doses of Dengvaxia, an anti-dengue vaccine. In a bulletin issued in December 2021, the PAO stated that 75 civil cases involving Dengvaxia had been lodged before the Quezon City Regional Trial Court.
Dengvaxia Vaccine News
March 22, 2024 - A research study published by The Lancet Infectious Diseases investigated the effects of prematurely discontinued CYD-TDV vaccinations on children's susceptibility to the dengue virus.
August 8, 2023 - The U.S. FDA reissued STN: 125682.
June 30, 2023 - The U.S. FDA issued a Supplemental Approval to Sanofi Pasteur, Inc., Attention: Michael F. Stirr.
January 28, 2023 - Pharmacies in Costa Rica offer the Dengvaxia vaccine for over $100 per dose.
October 20, 2022 - The U.S. CDC presented: UPDATE ON DENGVAXIA: EFFICACY, SAFETY, AND IMPLEMENTATION.
June 29, 2022 - A new study published by Science.org concluded, 'These data suggest that E- and NS1-specific Fc functions may serve as correlates of protection, which can be potentially applied toward the design and evaluation of dengue vaccines.'
April 26, 2022 - The Philippines Department of Health launched the Chikiting Bakunation Days. This annual vaccination drive aims to reach at least one million children who have missed out and are yet to receive any routine vaccine.
December 17, 2021 - The U.S. CDC vaccine committee recommended using Dengvaxia with specific restrictions. The vaccine should only be used for those aged 9–16 who live in endemic areas and have evidence with a specific diagnostic test of prior dengue infection.
December 16, 2021 - The JAMA Network published a viewpoint discussing various challenges to broadly deploying the Dengvaxia vaccine.
July 15, 2021 - The media reported Sanofi had sought permission to market the Dengvaxia vaccine in India.
June 24, 2021 - The U.S. CDC's ACIP committee presented the 'Dengvaxia Vaccine Knowledge and Attitudes Survey- Puerto Rico Physicians.' The ACIP voted 14-0 to adopt the new recommendations.
June 24, 2021 - The journal Nature published a study: Evaluation of the extended efficacy of the Dengvaxia vaccine against symptomatic and subclinical dengue infection.... the vaccine's protective effect was concentrated in the first three years following vaccination. Among individuals with the same antibody titer, we found no difference between the risk of subsequent infection or disease between placebo and vaccine recipients, suggesting that antibody titers are a good predictor of protection and disease risk.
June 1, 2021 - The Manila Public Attorney's Office reported that a 14-year-old boy from Cavite died of complications from the Dengvaxia vaccine.
May 5, 2021 - The U.S. CDC's ACIP presented the importance of a specific test for pre-vaccination screening. ACIP explores whether three doses of Dengvaxia should be administered routinely to persons 9–16 years of age with laboratory-confirmed previous dengue infection and living in endemic areas, such as Puerto Rico.
November 17, 2020 - Study published by The Lancet: A 2-dose CYD-TDV regimen might be an alternative to the licensed 3-dose regimen in dengue seropositive individuals at baseline and aged nine years and older. Vaccination with reduced doses could improve vaccine compliance and coverage, especially in low-resource settings.
November 16, 2020 - Study: Accuracy and efficacy of pre-dengue vaccination screening for previous dengue infection with five commercially available immunoassays: a retrospective analysis of phase 3 efficacy trials. Our findings suggest that these immunoassays could be used for pre-vaccination screening for CYD-TDV as tools to assist risk stratification until more sensitive and convenient tests become available.
October 16, 2020 - The Philippines Supreme Court has approved the petition to transfer all Dengvaxia-related cases to a single Regional Trial Court.
December 27, 2019 - A study reported on December 27, 2019, that the 'screen and vaccinate' strategy effectively reduces the number of hospitalized and severe dengue cases.
March 7, 2019 - The U.S. FDA approved the use of Dengvaxia for children ages 9-16.
December 19, 2018 - The European Commission has granted marketing authorization for Dengvaxia®.
September 7, 2018 - The WHO issued a paper on dengue vaccines.
February 1, 2018 - Editorial published by The Lancet: The dengue vaccine dilemma.
October 4, 2016 - Sanofi Pasteur announced that Dengvaxia had received market approval in Mexico, the Philippines, Brazil, El Salvador, Costa Rica, Paraguay, Guatemala, Peru, Indonesia, Thailand, and Singapore.
December 23, 2015 - The Philippines became the first Asian country to approve the commercial sale of Dengvaxia. In April 2016, the Department of Health launched the dengue vaccination campaign in central Luzon, Calabarzon, and Metro Manila, where about 700,000 individuals received at least one vaccine dose.
September 14, 2014 - The Lancet: the past decade has also seen an upsurge in research on dengue virology, pathogenesis, and immunology, and the development of antivirals, vaccines, and new vector-control strategies that can positively impact dengue control and prevention.
Dengvaxia Dengue Vaccine Clinical Trials
Dengvaxia is currently involved in several different clinical trials.