CD8 T cell responses to live, viral Yellow fever vaccine in humans

Abstract

Yellow Fever virus 17D (YFV‐17D) is a live attenuated vaccine that generates long‐lasting protective immunity. It provides an invaluable model to study CD8 T cell differentiation in a primary, acute viral infection in humans. Using a comprehensive peptide library spanning the viral polyprotein, we report an analysis of the YFV‐17D specific primary CD8 T cell response in vaccinated subjects. The largest proteins NS3, NS5 and Env accounted for the majority of the response. Identification of an immunodominant HLA‐0201 restricted CD8 T cell epitope enabled longitudinal phenotypic and functional analysis of antigen specific CD8 T cells in response to YFV‐17D. Effector CD8s seen as early as 11 days post vaccination till as late as 21 days upregulated proliferation (Ki‐67) and activation (HLA‐DR, CD38) markers and acquired cytolytic molecules like granzyme B. These markers were downregulated by day 30 after which a contraction of tetramer specific cells was seen. In short‐term in vitro stimulations of PBMCs with peptide, antigen experienced CD8 T cells were capable of producing cytokines like IFNγ, TNFα and IL‐2, chemokines like Mip‐1β and showed degranulation indicating that the vaccine elicits a polyfunctional CD8 response similar to vaccinia, another successful live viral vaccine. Evaluating the quality of the response may reveal the immune mechanisms responsible for an effective vaccine.