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 ORCID: https://orcid.org/0000-0002-9856-2938, McLaren, James E. ORCID: https://orcid.org/0000-0002-7021-5934, Price, David A. ORCID: https://orcid.org/0000-0001-9416-2737, 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:	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:	08 May 2023 02:32
URI:	https://orca.cardiff.ac.uk/id/eprint/149831

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