@article{de7a212ee98348598fba037b8a6667c3,
title = "Human CD4+ T cell responses to an attenuated tetravalent dengue vaccine parallel those induced by natural infection in magnitude, HLA restriction, and antigen specificity",
abstract = "Dengue virus (DENV) is responsible for growing numbers of infections worldwide and has proven to be a significant challenge for vaccine development. We previously demonstrated that CD8+ T cell responses elicited by a dengue live attenuated virus (DLAV) vaccine resemble those observed after natural infection. In this study, we screened peripheral blood mononuclear cells (PBMCs) from donors vaccinated with a tetravalent DLAV vaccine (TV005) with pools of dengue virusderived predicted major histocompatibility complex (MHC) class II binding peptides. The definition of CD4+ T cell responses after live vaccination is important because CD4+ T cells are known contributors to host immunity, including cytokine production, help for CD8+ T and B cells, and direct cytotoxicity against infected cells. While responses to all antigens were observed, DENV-specific CD4+ T cells were focused predominantly on the capsid and nonstructural NS3 and NS5 antigens. Importantly, CD4+ T cell responses in vaccinees were similar in magnitude and breadth to those after natural infection, recognized the same antigen hierarchy, and had similar profiles of HLA restriction. We conclude that TV005 vaccination has the capacity to elicit CD4+ cell responses closely mirroring those observed in a population associated with natural immunity.",
keywords = "CD4, CD4 T cell, Dengue virus, HLA, Live attenuated, Live attenuated vaccine, MHC, T cells, TV005, tetravalent, vaccines",
author = "Angelo, {Michael A.} and Alba Grifoni and O'Rourke, {Patrick H.} and John Sidney and Sinu Paul and Bjoern Peters and {de Silva}, {Aruna D.} and Elizabeth Phillips and Simon Mallal and Diehl, {Sean A.} and Kirkpatrick, {Beth D.} and Whitehead, {Stephen S.} and Durbin, {Anna P.} and Alessandro Sette and Daniela Weiskopf",
note = "Funding Information: We thank all study participants and the University of Vermont Vaccine Testing Center, Center for Immunization Research at the Johns Hopkins School of Public Health, and General Clinical Research Center teams for their invaluable participation. Finally, we thank the National Blood Center, Ministry of Health, Colombo, Sri Lanka, for providing the buffy coat samples used in this study. M.A.A. and P.H.O. performed experiments, reviewed data, and planned experimental strategy. A.G., J.S., S.P., and B.P. performed bioinformatics analyses. A.D.D.S. performed comparisons to natural infection data. E.P. and S.M. performed and coordinated HLA typing and related analysis. S.S.W. developed and provided the tetravalent DLAV and analyzed data from the clinical studies. B.D.K., A.P.D., and S.A.D. performed the clinical studies and obtained the PBMC donations analyzed. A.S. and D.W. designed, conducted, and supervised the overall study. All authors participated in the writing and editing of the manuscript. We declare that we have no conflicts of interest. This work was supported by National Institutes of Health contracts HHSN272200900042C and HHSN27220140045C (to A.S.), by BMGF grant OPP1104710 (to A.P.D.), and by the Intramural Research Program of the NIH National Institute of Allergy and Infectious Diseases. Publisher Copyright: {\textcopyright} 2017 American Society for Microbiology.",
year = "2017",
doi = "10.1128/JVI.02147-16",
language = "English (US)",
volume = "91",
journal = "Journal of virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "5",
}