Evaluation of Live Attenuated Vaccines for Dengue and Zika Viruses (and their Challenge Models)
Stephen Whitehead, NIAID, National Institutes of Health, USA
An effective vaccine for universal control of dengue is a public health priority and several vaccine approaches have progressed into late stage development. We have even recently seen the launch of a vaccine for limited use under specific conditions (Dengvaxia). The goal of the NIAID dengue vaccine program remains focused on the development of a single-dose, live-attenuated tetravalent dengue vaccine that is safe, immunogenic in all populations, efficacious, and cost-effective. Adult cohort studies in the US among DENV-naïve subjects have demonstrated that the vaccine is safe and fully infectious following a single subcutaneous dose with >90% of subjects seroconverting to all four DENV serotypes. Vaccine infectivity studies support the use of the vaccine in naïve subjects. The vaccine elicits both a balanced neutralizing antibody response as well as a robust CD8+ T-cell repertoire and provides near sterilizing immunity against experimental challenge DENV infections. Adult cohort studies in Brazil, Thailand, and Bangladesh in dengue-experienced populations have demonstrated the favorable safety profile of the vaccine remains unchanged compared to that observed in DENV-naïve adult subjects. The vaccine has been evaluated in progressively younger subjects in Thailand, including adolescents (13 - 17 years old), children (5 - 12 years old), and younger children (1 - 4 years old). A pivotal Phase 3 study across Brazil is ongoing under the direction of the Butantan Institute in Sao Paulo. The laboratory team at LVD/NIAID is now leveraging their experience with the live attenuated DENV vaccine to develop vaccines for Zika virus.
Funding provided by the Intramural Research Program of the NIAID, NIH, USA.
Credits: None available.
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