The immunogenicity of an HIV-1 Gag conserved element DNA vaccine in people with HIV and receiving antiretroviral therapy

AIDS. 2024 Jun 1;38(7):963-973. doi: 10.1097/QAD.0000000000003804. Epub 2023 Dec 1.

Abstract

Objective: The primary objective of the study was to assess the immunogenicity of an HIV-1 Gag conserved element DNA vaccine (p24CE DNA) in people with HIV (PWH) receiving suppressive antiretroviral therapy (ART).

Design: AIDS Clinical Trials Group A5369 was a phase I/IIa, randomized, double-blind, placebo-controlled study of PWH receiving ART with plasma HIV-1 RNA less than 50 copies/ml, current CD4 + T-cell counts greater than 500 cells/μl, and nadir CD4 + T-cell counts greater than 350 cells/μl.

Methods: The study enrolled 45 participants randomized 2 : 1 : 1 to receive p24CE DNA vaccine at weeks 0 and 4, followed by p24CE DNA admixed with full-length p55 Gag DNA vaccine at weeks 12 and 24 (arm A); full-length p55 Gag DNA vaccine at weeks 0, 4, 12, and 24 (arm B); or placebo at weeks 0, 4, 12, and 24 (arm C). The active and placebo vaccines were administered by intramuscular electroporation.

Results: There was a modest, but significantly greater increase in the number of conserved elements recognized by CD4 + and/or CD8 + T cells in arm A compared with arm C ( P = 0.014). The percentage of participants with an increased number of conserved elements recognized by T cells was also highest in arm A (8/18, 44.4%) vs. arm C (0/10, 0.0%) ( P = 0.025). There were no significant differences between treatment groups in the change in magnitude of responses to total conserved elements.

Conclusion: A DNA-delivered HIV-1 Gag conserved element vaccine boosted by a combination of this vaccine with a full-length p55 Gag DNA vaccine induced a new conserved element-directed cellular immune response in approximately half the treated PWH on ART.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Clinical Trial, Phase II
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines* / administration & dosage
  • AIDS Vaccines* / immunology
  • Adult
  • Anti-Retroviral Agents / therapeutic use
  • CD4 Lymphocyte Count
  • Double-Blind Method
  • Electroporation
  • Female
  • HIV Infections* / drug therapy
  • HIV Infections* / immunology
  • HIV-1* / genetics
  • HIV-1* / immunology
  • Humans
  • Injections, Intramuscular
  • Male
  • Middle Aged
  • Placebos / administration & dosage
  • Treatment Outcome
  • Vaccines, DNA* / administration & dosage
  • Vaccines, DNA* / immunology
  • Viral Load
  • gag Gene Products, Human Immunodeficiency Virus* / genetics
  • gag Gene Products, Human Immunodeficiency Virus* / immunology

Substances

  • Vaccines, DNA
  • AIDS Vaccines
  • gag Gene Products, Human Immunodeficiency Virus
  • Anti-Retroviral Agents
  • Placebos