Vaccine Info

Dengvaxia Dengue Vaccine

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May 24, 2022
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Dengvaxia (CYD-TDV) Dengue Vaccine Description 2022

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 indicated for dengue disease prevention, caused by dengue virus serotypes 1, 2, 3, and 4. In 2015, Sanofi Pasteur introduced the first dengue vaccine, which is registered in several of the most endemic countries in the world. Sanofi announced in 2017 that people who receive the vaccine and have not been previously infected with a dengue virus might be at risk of developing severe dengue if they get dengue after being vaccinated. Dengvaxia is not approved for use in individuals not previously infected by any of the dengue virus four serotypes or for whom their immunization information is unknown. According to the WHO, there is no specific treatment for dengue/severe dengue.

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 (the US territories of American Samoa, Puerto Rico, and the U.S. Virgin Islands), with laboratory-confirmed prior dengue virus infection. On January 22, 2020, the FDA approved the Sanofi Pasteur Inc. request submitted on July 23, 2019, to supplement the Dengvaxia Biologics License Application. In addition, subgroup vaccine information was also updated.

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. The CDC confirmed on December 17, 2021 - Recommendations of the Advisory Committee on Immunization Practices, U.S.

The Lancet published a peer-reviewed study on March 29, 2022, that assessed the need for a CYD-TDV booster after these primary vaccination regimens. This phase 2 study funded by Sanofi concluded that CYD-TDV booster one year or two years after the two-dose or three-dose primary vaccination regimen does not elicit a consistent, meaningful booster effect against all dengue serotypes in participants seropositive for dengue at baseline.

Dengvaxia - NDC CODE: 49281-605UNII 75KB2HPX5HU.S. License No. 1725; EMA: EMEA/H/C/004171

Sanofi Pasteur Inc. (SNY) is the manufacturer of the Dengvaxia vaccine. Sanofi U.S. Headquarters is located at 55 Corporate Drive, Bridgewater, NJ 08807.

Dengvaxia Dengue Vaccine Indication For 2022

Dengvaxia is the only dengue vaccine approved by the U.S. FDA and recommended for routine use by the CDC's Advisory Committee on Immunization Practices. Dengvaxia is indicated for use in individuals with laboratory-confirmed previous dengue infection and living in endemic areas, says the CDC. The vaccine is available for the U.S. territories of American Samoa, Puerto Rico, the U.S. Virgin Islands, and freely associated states, including the Federated States of Micronesia, the Republic of Marshall Islands, and the Republic of Palau. The vaccine is not approved for use in U.S. travelers visiting but not living in an area where dengue is common.

Dengvaxia increases the risk for severe dengue in those who experience their first natural infection after vaccination. The most important adverse event is hospitalization or severe dengue after vaccinating a seronegative person misclassified as a seropositive.

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 additional vaccine-associated hospitalization.

And a previous infection with the Zika virus, common in areas where dengue is endemic, can also increase the risk of symptomatic and severe dengue for subsequent infections.

Dengvaxia Dengue 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). The CDC published updated vaccination schedules for 2022, which do not indicate any Dengvaxia coadministration advisories.

On March 29, 2022, the peer-review journal The Lancet reported 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 booster effect against all dengue serotypes in participants who are seropositive for dengue at baseline.'

Dengvaxia Dengue Vaccine Limitation of Use For 2022

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. When an individual is infected with one dengue serotype, subsequent infection with another serotype may result in more intense infections. 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. 

Pregnant females, who are at increased risk for dengue-related complications, were not specifically studied in the Dengvaxia trial, says the CDC. 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 not sufficient to determine a possible effect of Dengvaxia on pregnancy. And data are not available to evaluate the safety of Dengvaxia in breastfeeding infants. The developmental and health benefits of breastfeeding should be considered in conjunction with the risk for DENV infection in the mother and infant.

And the safety and efficacy of Dengvaxia have not been assessed in persons with HIV infection. However, ongoing clinical studies assess the vaccine's use in adults with well-controlled HIV infection.

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 Dengue Vaccine Dosage

Dengvaxia (CYD-TDV) is given a 3-dose series six months apart (at months 0, 6, and 12). It is administered as a subcutaneous Injection.

On November 16, 2020, a study published by The Lancet found that 'A two-dose CYD-TDV regimen might be an alternative to the licensed three-dose regimen in individuals who are dengue seropositive at baseline and aged nine years and older. Vaccination with a reduced number of doses could improve vaccine compliance and coverage, especially in low-resource settings.' Sanofi Pasteur funded this study.

Dengvaxia Dengue Vaccine Side Effects

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).

Dengue Endemic Areas

Dengue epidemics occur in a cyclical pattern every 3 to 7 years, with all four DENV serotypes reported in the Pacific Islands and the Caribbean. Of areas where dengue is endemic, Puerto Rico, the U.S. Virgin Islands, and American Samoa report dengue cases to ArboNET. Approximately 90% of the population at risk for dengue in the U.S. territories and freely associated states live in Puerto Rico. From 2010–to 2020, approximately 95% of locally acquired dengue cases in the U.S. (n = 31,289) occurred in Puerto Rico (n = 29,779). During the same period, the greatest number of cases and hospitalizations in Puerto Rico occurred among persons aged 10–19 years, with approximately 11,000 reported cases and 4,000 hospitalizations. 

On April 14, 2022, Singapore's National Environment Agency confirmed dengue virus serotype 3 (DENV-3) had been detected in 24 of the 33 dengue clusters.

Dengvaxia Dengue Vaccine Pre-Vaccination 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 are shown by researchers to be highly expressed in patients that later develop serious symptoms.

The peer-review 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. And on May 2, 2022, The Lancet published a retrospective analysis of phase 3 efficacy trials that concluded the OnSite IgG RDT test should provide a valuable tool for screening for previous dengue infection at the point of vaccination.

Dengvaxia 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, PAO said there are now 75 civil cases involving Dengvaxia lodged before the Quezon City regional trial court.

    Dengvaxia Dengue Vaccine News

    May 16, 2022 - National Dengue Day 2022 is celebrated in India to spread awareness of the disease and provide preventive methods as well as tips to treat dengue.

    May 5, 2022 - The ECDC reported 785,736 cases and 588 deaths have been reported in 2022.

    April 26, 2022 - The Philippines Department of Health launched the Chikiting Bakunation Days, an annual vaccination drive that aims to reach at least one million children who have missed out and are yet to receive any routine vaccine.

    March 17, 2022 - The South Delhi Municipal Corporation confirmed that New Delhi recorded 9,613 dengue cases and 23 fatalities in 2021, making it the second-worst outbreak. Dengue was declared a "notifiable disease" under the Epidemic Diseases Act on October 14, 2021.

    March 7, 2022 - Local media confirmed India reported 1,23,106 dengue cases and 90 deaths in 2021.

    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 deploying the Dengvaxia vaccine broadly.

    August 14, 2021 - The WHO's PAHO dashboard data indicates the USA has reported (28), and Brazil confirmed over 750,000 dengue cases during 2021.

    August 11, 2021 - The U.S. CDC confirmed the total number of dengue cases during 2021: US States: 28 dengue cases reported; US Territories: 347 dengue cases reported (Puerto Rico 346).

    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 protective effect of the vaccine 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 both protection and disease risk. 

    June 1, 2021 - The Manila Public Attorney's Office reported a 14-year-old boy from Cavite died of complications attributed to the controversial 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.

    April 28, 2021 – Sanofi reported quarterly earnings: Travel and other endemic vaccine sales decreased 37.4%.

    April 1, 2021 - Report: Sanofi has shown concern about climate change and health, especially for the most vulnerable populations, and works to address the challenges with a particular focus on two main health consequences of climate change: evolution of vector-borne diseases and indoor and outdoor air pollution and respiratory allergies.

    April 1, 2021 - Réunion is reporting an epidemic accelerating on the island. March 15-21, 758 cases of dengue have been confirmed. As of this date, only serotype one has been detected in the confirmed cases.

    March 2, 2021 - The U.S.CDC issued a Level 1 Travel Alert for many parts of Central and South America, Mexico, and the Caribbean regarding Dengue virus risks. Because mosquito bites spread dengue, all travelers should prevent mosquito bites to risk areas.

    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 individuals who are dengue seropositive at baseline and aged 9 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.

    October 14, 2020 - The U.S. CDC reissued a Travel Alert for the Americas regarding various Dengue outbreaks. Dengue is an ongoing risk in many parts of Central and South America, Mexico, and the Caribbean. Travelers to areas of risk should protect themselves by preventing mosquito bites. Also, the countries listed below are reporting higher-than-usual numbers of dengue cases.

    September 30, 2020 - Dengue is an ongoing risk in many parts of Africa and the Middle East. Travelers to areas of risk should protect themselves by preventing mosquito bites.

    September 30, 2020 - Dengue is an ongoing risk in many parts of Asia and the Pacific Islands. Travelers to areas of risk should protect themselves by preventing mosquito bites. Also, the countries listed are reporting higher-than-usual dengue cases, and travelers visiting these countries may be at increased risk.

    July 2, 2020 - The U.S. CDC reported the US States had confirmed 124 dengue cases, and the US Territories have reported 218 dengue cases during 2020.

    June 23, 2020 - More than 1.6 million dengue cases have been reported in the Americas in the first five months of 2020, drawing attention to the need to continue eliminating mosquito vectors of disease even in the midst of the COVID-19 pandemic.

    June 9, 2020 - To notify visitors of their health risks when visiting the Americas, the US CDC reissued a Level 1 Travel Alert. Dengue is an ongoing risk in many parts of Central and South America, Mexico, and the Caribbean (map). Travelers to areas of risk should protect themselves by preventing mosquito bites. 

    May 21, 2020 - The CDC issued a Travel Alert which says 'Dengue is a risk in many parts of Central and South America, Mexico, and the Caribbean.'

    January 22, 2020 - The US FDA 'approved your request submitted and received on July 23, 2019, to supplement your Biologics License Application (BLA) under section 351(a) of the Public Health Service Act for Dengue Tetravalent Vaccine, Live (DENGVAXIA) to revise the NDC number for the Saline Diluent and update the package insert and diluent container labeling to include the new NDC number.'

    December 27, 2019 - A study reported on December 27, 2019, the 'screen and vaccinate' strategy effectively reduces the number of hospitalized and severe dengue cases. The World Health Organization (WHO) recommended the option of a dengue screen and vaccination policy is likely to have a positive impact both at the individual and population level, across a wide range of transmission settings. The WHO screen and vaccinate intervention model was cost-effective in all countries, except for reduced transmission settings. The overall population impact of a screen and vaccinate approach is also likely to be improved by using several rounds of screening (up to 48% reduction in dengue hospitalization over 10 years with 5 rounds).

    May 1, 2019 - Division of Vaccines and Related Product Applications Office of Vaccines Research and Review.

    March 7, 2019 - The U.S. FDA approved the use of Dengvaxia for children ages 9-16 and is considered a significant medical advance in dengue prevention, which is considered an unmet medical need by the FDA. In addition, the European Commission has granted marketing authorization for Dengvaxia, Sanofi's dengue vaccine. The marketing authorization follows the October 18, 2018, recommendation by the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) to approve the dengue vaccine in European endemic areas. Dengvaxia will be available in Europe to prevent dengue disease in individuals 9-45 years of age with a documented prior dengue infection and who live in endemic areas.

    December 19, 2018 - The European Commission has granted marketing authorization for Dengvaxia®, Sanofi's dengue vaccine. The marketing authorization follows the October 18, 2018, recommendation by the European Medicines Agency's Committee for Medicinal Products for Human Use to approve the dengue vaccine in European endemic areas.

    September 7, 2018 - The WHO issued a position paper regarding 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 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 regions 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.

    Dengue Diagnostic Tests

    Testing is available to determine a previous dengue infection. Non-FDA tests may yield false-positive results (e.g., due to cross-reactivity with other flaviviruses).

    Dengvaxia Dengue Vaccine Clinical Trials

    Dengvaxia is currently involved in several different clinical trials.

     

    Clinical Trials