Human CD4+ T cell responses to an attenuated tetravalent dengue vaccine parallel those induced by natural infection in magnitude, HLA restriction, and antigen specificity

Michael A. Angelo, Alba Grifoni, Patrick H. O'Rourke, John Sidney, Sinu Paul, Bjoern Peters, Aruna D. de Silva, Elizabeth Phillips, Simon Mallal, Sean A. Diehl, Beth D. Kirkpatrick, Stephen S. Whitehead, Anna P. Durbin, Alessandro Sette, Daniela Weiskopf

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere02147-16
JournalJournal of virology
Volume91
Issue number5
DOIs
StatePublished - 2017
Externally publishedYes

Keywords

  • CD4
  • CD4 T cell
  • Dengue virus
  • HLA
  • Live attenuated
  • Live attenuated vaccine
  • MHC
  • T cells
  • TV005
  • tetravalent
  • vaccines

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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