Preexisting memory CD4+ T cells contribute to the primary response in an HIV-1 vaccine trial.
(Journal Article;Multicenter Study)
Naive and memory CD4+ T cells reactive with human immunodeficiency virus type 1 (HIV-1) are detectable in unexposed, unimmunized individuals. The contribution of preexisting CD4+ T cells to a primary immune response was investigated in 20 HIV-1-seronegative volunteers vaccinated with an HIV-1 envelope (Env) plasmid DNA prime and recombinant modified vaccinia virus Ankara (MVA) boost in the HVTN 106 vaccine trial (clinicaltrials.gov NCT02296541). Prevaccination naive or memory CD4+ T cell responses directed against peptide epitopes in Env were identified in 14 individuals. After priming with DNA, 40% (8/20) of the elicited responses matched epitopes detected in the corresponding preimmunization memory repertoires, and clonotypes were shared before and after vaccination in 2 representative volunteers. In contrast, there were no shared epitope specificities between the preimmunization memory compartment and responses detected after boosting with recombinant MVA expressing a heterologous Env. Preexisting memory CD4+ T cells therefore shape the early immune response to vaccination with a previously unencountered HIV-1 antigen.
Campion, SL; Brenna, E; Thomson, E; Fischer, W; Ladell, K; McLaren, JE; Price, DA; Frahm, N; McElrath, JM; Cohen, KW; Maenza, JR; Walsh, SR; Baden, LR; Haynes, BF; Korber, B; Borrow, P; McMichael, AJ
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