Dissecting antibodies induced by a chimeric yellow fever-dengue, live-attenuated, tetravalent dengue vaccine (CYD-TDV) in naïve and dengue exposed individuals

Sanofi Pasteur has developed a chimeric yellow fever-dengue, live-attenuated, tetravalent dengue vaccine (CYD-TDV) that is currently approved for use in several countries. In clinical trials, CYD-TDV was efficacious at reducing laboratory-confirmed cases of dengue disease. Efficacy varied by dengue virus (DENV) serotype and pre-vaccination dengue immune status. We compared the properties of antibodies in naïve and DENV exposed individuals who received CYD-TDV. We depleted specific populations of DENV-reactive antibodies from immune sera to estimate the contribution of serotype-cross reactive and type-specific antibodies to neutralization. Subjects with no pre-existing immunity to DENV developed neutralizing antibodies to all 4 serotypes of DENV. Further analysis demonstrated that DENV4 was mainly neutralized by type-specific antibodies whereas DENV1, 2 and 3 were mainly neutralized by serotype cross-reactive antibodies. When subjects who had pre-existing immunity to DENV were vaccinated, they developed higher levels of neutralizing antibodies compared to naïve subjects who were vaccinated. In pre-immune subjects CYD-TDV boosted cross-reactive neutralizing antibodies, while maintaining type-specific neutralizing antibodies acquired before vaccination. Our results demonstrate that the quality of neutralizing antibodies induced by CYD-TDV varies depending on DENV serotype and previous immune status. We discuss the implications of these results for understanding vaccine efficacy.