Vaccine for Dengue (Dengvaxia CYD-TDV)

R. Gobinathan*

Junior Clinical Pharmacist, Kauvery Hospital, Cantonment, India

*Correspondence: clinical.cst@kauveryhospital.com

Aim

The objective of this paper is to present an overview of the first dengue vaccine Dengvaxia (CYD-TDV) and its therapeutic application.

Dengvaxia

Dengvaxia is a vaccine used to protect against dengue disease in people aged 6 to 45 years of age, with test-confirmed previous dengue infection, approved by Europian Medical Agency (EMA), and individuals 9 through 16 years of age with laboratory-confirmed previous dengue infection and living in endemic areas, by FDA.

Dengue disease is a mosquito-borne tropical disease caused by the dengue virus, leading to mild, flu-like symptoms in most people. However, a small number of patients develop severe disease, with potentially fatal bleeding and organ damage. The risk of severe disease is higher in people who have been infected a second time. There are several varieties (called serotypes) of dengue virus and Dengvaxia protects against serotypes 1, 2, 3 and 4 [1]

Limitations of use

Dengvaxia is not approved for use in individuals not previously infected by dengue. Those not previously infected are at increased risk for severe dengue disease when vaccinated and subsequently infected with dengue virus.

Action

Dengvaxia is a tetravalent vaccine, live, for the prevention of dengue disease caused by serotypes 1 – 4 of the virus. Dengvaxia elicits dengue-specific immune responses against the four dengue virus serotypes. The exact mechanism of protection has not been determined [2]. Dengvaxia contains weakened viruses that do not cause disease. When a person is given the vaccine, the immune system recognizes the dengue proteins in the weakened viruses as ‘foreign’ and makes antibodies against them.

Dosage and administration

Dengvaxia should be administered as 3 doses (0.5 mL each) 6 months apart (at months 0, 6, and 12). After reconstitution, 0.5 mL of Dengvaxia should be immediately administered subcutaneous route. Dengvaxia is for subcutaneous use only. Dengvaxia should not be administered by intramuscular injection [3].

Adverse reactions

The most frequently reported adverse reactions regardless of the dengue serostatus prior to vaccination were headache (40%), injection site pain (32%), malaise (25%), asthenia (25%), and myalgia (29%) [4].

Current scenario of dengue vaccines

Developing an effective vaccine against dengue is challenging due to the fact that the DENV has four serotypes, with all four types having the ability to cause disease.

current-scenario-of-dengue-vaccines

Shown above is the image of several other dengue vaccines undergoing clinical evaluation. So far, Dengvaxia is the only vaccine licensed and it is used in many countries worldwide since 2015. Only dengue antigen vaccines are available for dengue infections; dengue antibody vaccines are not available.

History

The first dengue vaccine, Dengvaxia (CYD-TDV), developed by Sanofi Pasteur, was licensed in December 2015 and approved by US FDA in ~20 countries. In November 2017, the results of an additional analysis to retrospectively determine serostatus at the time of vaccination were released. The analysis showed that if a person who has never had dengue is given Dengvaxia and gets infected with dengue again later they’re at risk for hospitalization and severe, life-threatening disease [5].

Dengvaxia in India

There is no vaccine for dengue yet introduced in India. India has completed all animal trials and is now granted permission for human trials. Pharmaceutical companies and vaccine makers who have developed potential vaccine candidates against dengue and have successfully completed phase 1 and 2 clinical trials can submit their expressions of interest (EoI) to ICMR by 11 March 2022[6]. The phase-3 clinical trials will be conducted in India.

The Dengvaxia vaccine is available in the United States for us children 9 through 16 years old with laboratory-confirmed evidence.

Official records show that there are two other dengue vaccine candidates being developed by Panacea Biotech Limited and Sanofi India Private Limited. Both have got permission for clinical trials. Panacea Biotech Limited has completed phase-1 and phase-2 trials. Sanofi India Private Limited’s vaccine has already been approved in the US; it has started conducting trials in India [7]. So, the dengue vaccine may come soon in India.

The co-founder of Infosys, NR Narayana Murthy, acknowledged the advancements in science and technology over the past two decades but bemoaned the absence of an Indian company among the world’s top 250 research institutions and the inability of the nation to produce vaccines for diseases like dengue and chikungunya.

Murthy claimed that in 2022, the nation made healthy strides in both science and technology, rolling out two Indian companies’ Covid 19 vaccinations for a billion Indians

Murthy added that these are all positive developments that demonstrate India is moving forward. But there are still some difficulties. Still, not a single higher education institution from India is listed among the top 250 worldwide in the 2022 global ranking.

He lamented saying that even vaccines we have produced are either based on Technologies from other advanced countries or research from the developed world.

He concluded by stating that we have still not produced a vaccine for dengue and chikungunya, which have been ravaging us for 70 years [8].

Test before vaccination

Laboratory confirmation of previous dengue virus infection is required and can be obtained by

  • Positive dengue RT-PCR test result, or
  • Positive dengue NS1 antigen test result or positive results on both of the following
  • Anti-Dengue Virus NS1 Type 1-4 ELISA (IgG)
  • Dengue IgG Rapid Test

A single positive anti-dengue virus immunoglobulin M test result is not sufficient proof of dengue virus infection for a vaccination with dengvaxia due to potential cross-reactivity with other circulating flaviviruses (e.g Zika virus) in dengue-endemic areas. [9]

Conclusion

Dengvaxia is currently indicated in most countries for individuals 9 years of age and older living in a dengue-endemic area. In this indicated population, Dengvaxia has been shown to prevent 93% of severe diseases and 80% of hospitalizations due to dengue.

NOTE: In 2022, a new second dengue vaccine (TAK-003) is a dengue tetravalent vaccine (live, attenuated), manufactured by Takeda. Takeda announced that the US Food and Drug Administration (FDA) has accepted and granted priority review of the Biologics License Application (BLA) for TAK-003, the company’s investigational dengue vaccine candidate. In the US, TAK-003 is being evaluated for the prevention of dengue disease caused by any dengue virus serotype in individuals four years through 60 years of age. In October 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the approval of Takeda’s dengue vaccine candidate, TAK-003, for the prevention of dengue disease caused by any serotype in individuals four years of age and older in Europe and dengue-endemic countries. Currently, TAK-003 has not been approved by the FDA. India is not a part of the global phase 3-trial of the Takeda dengue vaccine, which means as per local regulation it will have to conduct a bridging trial to assess the safety and efficacy of the vaccine in the local population [10].

References

ps://www.centerwatch.com/directories/1067-fda-approved-drugs/listing/3381-dengvaxia-dengue-tetravalent-vaccine-live https://www.cdc.gov/mmwr/volumes/70/rr/pdfs/rr7006a1-h.pdf https://www.fda.gov/media/124379/download

    1. WHO. Dengue and severe dengue Fact Sheet.

https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue https://www.livemint.com/science/health/india-set-to-carry-out-phase-3-clinical-trials-for-vaccine-against-dengue-11646595145856.html https://indianexpress.com/article/lifestyle/health/manufacturer-phase-1-trial-of-dengue-vaccine-gets-nod-8149543 https://timesofindia.indiatimes.com/city/bengaluru/no-indian-institution-is-in-top-250-weve-not-made-key-vaccines-says-nr-narayana-murthy/articleshow/95543472.cms https://www.cdc.gov/dengue/vaccine/parents/testing-before-vaccination.html https://health.economictimes.indiatimes.com/news/pharma/takedas-bla-for-tak-003-dengue-vaccine-candidate-gets-priority-review-by-fda/95711468 https://medicalxpress.com/news/2022-12-japanese-dengue-vaccine-eu.html?utm_source=nwletter&utm_medium=email&utm_campaign=daily-nwletter

R.-Gobinathan

R. Gobinathan

Junior Clinical Pharmacist

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