A Prime-Boost Dengue Vaccination Strategy Induces Durable Multivalent Memory B Cell Responses

Abstract

Abstract Denguevirus is a mosquito-borne flavivirus that is comprised of four antigenically related but distinct serotypes. A higher risk for the most severe clinical manifestations of dengue infection, dengue fever and dengue hemorrhagic fever, is associated with sequential infections with heterologous serotypes. While there currently is no precisely defined correlate of protection, durable tetravalent immunity is the desired outcome of dengue vaccination. A Phase 1 clinical trial was conducted at the Walter Reed ArmyInstitute of Research (WRAIR), WRAIR #2136, using live attenuated virus (LAV)and purified inactivated virus (PIV) vaccine candidates containing all fourserotypes. The two products were tested in a prime-boost regimen (PIV followed by LAV and vice versa) in different schedules to determine if dosing schedule or order of administration affected neutralizing antibody levels and/or cell mediated responses. Utilizing a three color Fluorospot assay to measure DENV-specific IgG, IgA, and IgM secreting cells, we tested 6-months post second dose memory B cell cultures to determine if the response was tetravalent and if a change in vaccination strategy affected the valency. We also investigated how memory B cell responses correlated to neutralizing antibody data. Results show that a majority of subjects have a robust multivalent DENV-specific IgG memory B cell response at 6 months post-vaccination. A better understanding of memory B cell responses and how they relate to neutralizing antibody will help find a suitable DENV vaccine that provides durable tetravalent immunity.