Dengue Vaccine : The Asian Concerns
Dr KK Aggarwal
President CMAAO and HCFI
The Health Minister Dr Harsh Wardhan told the parliament that India is near ready for the dengue vaccine. Let us know the facts
1. A live attenuated vaccine known as Dengvaxia, developed by Sanofi, was licensed in 2015. Following this, long-term follow-up of the Sanofi phase III efficacy trial participants has revealed potential safety concerns.
2. This vaccine, which appears to predispose dengue-naïve recipients to an increased risk of hospitalization in the future, is recommended by the WHO only for adults with a history of prior dengue virus infection.
3. India is poised now to test out two different dengue vaccine candidates in clinical trials in the near future, an LAV, TetraVax-DV, and a recombinant protein-based vaccine, DSV4.
4. All current tetravalent LAV approaches are based on physical mixtures of empirically determined amounts of four monovalent vaccine viruses. Such mixtures manifest a tendency of viral interference and could simulate a monotypic infection. In such a situation, seronegative recipients may be potentially sensitized to antibody-dependent enhancement (ADE) later in life, upon natural DENV infection.
1. Infection with one DENV type provides long-term protection against reinfection with that same type, supporting the feasibility of an effective dengue vaccine.
2. Also following infection with one type, there is short-lived immunity and cross-protection against disease caused by the other three DENV types.
3. But in view of the association between previous exposure to DENV types and severe disease, and the recognition that all four DENV types are capable of causing severe disease, ideally any candidate vaccine should produce protective immunity against all four DENV types (tetravalent immunity).
1. Can India afford ruling out prior infection in every case before giving the vaccine?
2. Will the tetravalent vaccine not produce ADE?
3. Will the vaccine be cost effective?
4. Given that the rate of clinically relevant third or fourth DENV infection is low, do we require tetravalent immunity?
5. Since waning immunity might also increase the risk for severe disease in vaccine recipients the aim should be only to have long lived vaccine-induced protective immunity.