Characterization of B-cell and T-cell responses to a tetravalent dengue purified inactivated vaccine in healthy adults

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Heather Friberg
Morgan Gargulak
Amanda Kong
Leyi Lin
Luis J. Martinez
Alexander C. Schmidt
Robert M. Paris
Richard G. Jarman
Clemente Diaz
Stephen J. Thomas
Philippe Moris
Jeffrey R. Currier
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[1] Walter Reed Army Institute of Research,Viral Diseases Branch
[2] GSK,undefined
[3] University of Puerto Rico School of Medicine,undefined
[4] GSK,undefined
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The increasing global impact of dengue underscores the need for a dengue virus (DENV) vaccine. We assessed B-cell and T-cell responses following vaccination with four formulations of a tetravalent dengue purified inactivated vaccine (DPIV) in dengue-primed and dengue-naive adults from two studies (NCT01666652, NCT01702857). Frequencies of DPIV-induced memory B cells specific to each DENV serotype remained high up to 12 months post-vaccination, and were higher in the dengue-primed than dengue-naive adults. A subsequent DPIV booster dose induced strong anamnestic B-cell responses. Multifunctional CD4+ T cells (predominantly expressing IL-2) were induced by DPIV, with higher frequencies in dengue-primed adults. DPIV-induced CD4+ T cells also demonstrated in vitro proliferative capacity and antigen-specific production of GM-CSF, IFN-γ, and IL-13. CD8+ T-cell responses were undetectable in dengue-naive adults and low in dengue-primed individuals. B- and T-cell responses persisted up to 12 months post-vaccination in both dengue-primed and dengue-naive adults.
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