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

Campion, Suzanne L., Brenna, Elena, Thomson, Elaine, Fischer, Will, Ladell, Kristin, McLaren, James E., Price, David A., Frahm, Nicole, McElrath, Juliana M., Cohen, Kristen W., Maenza, Janine R., Walsh, Stephen R., Baden, Lindsey R., Haynes, Barton F., Korber, Bette, Borrow, Persephone and McMichael, Andrew J. 2021. Preexisting memory CD4+ T cells contribute to the primary response in an HIV-1 vaccine trial. Journal of Clinical Investigation 131 (23) , e150823. 10.1172/JCI150823

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License
Publisher:	American Society for Clinical Investigation
ISSN:	1558-8238
Date of First Compliant Deposit:	23 May 2022
Date of Acceptance:	7 October 2021
Last Modified:	23 May 2022 14:30
URI:	https://orca.cardiff.ac.uk/id/eprint/149831

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