Journal article
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, Vol.91(5)
2016
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.
Details
- 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
- Authors/Creators
- M.A. Angelo (Author/Creator)A. Grifoni (Author/Creator)P.H. O'Rourke (Author/Creator)J. Sidney (Author/Creator)S. Paul (Author/Creator)B. Peters (Author/Creator)A.D. De Silva (Author/Creator)E. Phillips (Author/Creator)S. Mallal (Author/Creator)S.A. Diehl (Author/Creator)B.D. Kirkpatrick (Author/Creator)S.S. Whitehead (Author/Creator)A.P. Durbin (Author/Creator)A. Sette (Author/Creator)D. Weiskopf (Author/Creator)K. Frueh (Author/Creator)
- Publication Details
- Journal of Virology, Vol.91(5)
- Publisher
- American Society for Microbiology
- Identifiers
- 991005545264607891
- Copyright
- © 2017 American Society for Microbiology
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.228 Virology - Tropical Diseases
- 1.228.200 Mosquito-borne Viruses
- Web Of Science research areas
- Virology
- ESI research areas
- Microbiology