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

Journal Article · · Journal of Clinical Investigation
DOI:https://doi.org/10.1172/jci150823· OSTI ID:1879385
 [1];  [1];  [1];  [2];  [3];  [3];  [3];  [4];  [5];  [5];  [6];  [7];  [7];  [8];  [2];  [1];  [1]
  1. Univ. of Oxford (United Kingdom)
  2. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  3. Cardiff Univ., Wales (United Kingdom)
  4. Bill & Melinda Gates Medical Research Institute, Cambridge, MA (United States); Fred Hutchinson Cancer Research Center, Seattle, WA (United States)
  5. Fred Hutchinson Cancer Research Center, Seattle, WA (United States)
  6. Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States)
  7. Brigham and Women's Hospital (Harvard Medical School), Boston, MA (United States)
  8. Duke Univ., Durham, NC (United States)
+ Show Author Affiliations

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.

Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE; National Institutes of Health (NIH); Medical Research Council; Wellcome Trust
Grant/Contract Number:
89233218CNA000001
OSTI ID:
1879385
Report Number(s):
LA-UR-21-28624
Journal Information:
Journal of Clinical Investigation, Journal Name: Journal of Clinical Investigation Journal Issue: 23 Vol. 131; ISSN 0021-9738; ISSN 1558-8238
Publisher:
American Society for Clinical InvestigationCopyright Statement
Country of Publication:
United States
Language:
English

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