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Human CD4 + T Cell Responses to an Attenuated Tetravalent Dengue Vaccine Parallel Those Induced by Natural Infection in Magnitude, HLA Restriction, and Antigen Specificity

Angelo, M.A., Grifoni, A., O'Rourke, P.H., Sidney, J., Paul, S., Peters, B., De Silva, A.D., Phillips, E., Mallal, S., Diehl, S.A., Kirkpatrick, B.D., Whitehead, S.S., Durbin, A.P., Sette, A., Weiskopf, D. and Frueh, K. (2016) Human CD4 + T Cell Responses to an Attenuated Tetravalent Dengue Vaccine Parallel Those Induced by Natural Infection in Magnitude, HLA Restriction, and Antigen Specificity. Journal of Virology, 91 (5).

Link to Published Version: http://dx.doi.org/10.1128/JVI.02147-16
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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 virus-derived 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.

Publication Type: Journal Article
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Publisher: American Society for Microbiology
Copyright: © 2017 American Society for Microbiology
URI: http://researchrepository.murdoch.edu.au/id/eprint/35863
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