Preexisting memory CD4+ T cells contribute to the primary response in an HIV-1 vaccine trial
Suzanne L. Campion, … , Persephone Borrow, Andrew J. McMichael
Suzanne L. Campion, … , Persephone Borrow, Andrew J. McMichael
Published December 1, 2021
Citation Information: J Clin Invest. 2021;131(23):e150823. https://doi.org/10.1172/JCI150823.
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Concise Communication Clinical trials Immunology

Preexisting memory CD4+ T cells contribute to the primary response in an HIV-1 vaccine trial

Abstract

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.

Authors

Suzanne L. Campion, Elena Brenna, Elaine Thomson, Will Fischer, Kristin Ladell, James E. McLaren, David A. Price, Nicole Frahm, Juliana M. McElrath, Kristen W. Cohen, Janine R. Maenza, Stephen R. Walsh, Lindsey R. Baden, Barton F. Haynes, Bette Korber, Persephone Borrow, Andrew J. McMichael

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Figure 3

Epitope specificity of preimmunization and postvaccination Env-reactive CD4+ T cells.

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Epitope specificity of preimmunization and postvaccination Env-reactive ...
Postvaccination CD4+ T cell responses were mapped and quantified at V7 using ex vivo and cultured IFN-γ ELISpot assays. (A) Heatmaps showing the combined epitope mapping data from all volunteers at V7 (left) alongside a comparison with the epitope mapping data from all 20 volunteers at V2 (right). Ex vivo results are shown if both ex vivo and cultured data were available. Mean values are shown. SFU, spot-forming unit. (B) Identification of matching epitope-specific responses in the preimmunization and postvaccination repertoires of 4 donors immunized with ConS DNA. The scale for ex vivo and cultured data is shown on the left y axis, and the scale for naive (yellow) or memory (orange) precursor frequencies is shown on the right y axis. Mean ± SEM.