Non-HIV Vaccine-Induced Immune Responses as Potential Baseline Immunogenicity Predictors of ALVAC-HIV and AIDSVAX B/E-Induced Immune Responses

Viruses. 2024 Aug 27;16(9):1365. doi: 10.3390/v16091365.

Abstract

Identifying correlations between immune responses elicited via HIV and non-HIV vaccines could aid the search for correlates of HIV protection and increase statistical power in HIV vaccine-efficacy trial designs. An exploratory objective of the HVTN 097 phase 1b trial was to assess whether immune responses [focusing on those supported as correlates of risk (CoR) of HIV acquisition] induced via the RV144 pox-prime HIV vaccine regimen correlated with those induced via tetanus toxoid (TT) and/or hepatitis B virus (HBV) vaccines. We measured TT-specific and HBV-specific IgG-binding antibody responses and TT-specific and HBV-specific CD4+ T-cell responses at multiple time points in HVTN 097 participants, and we assessed their correlations at peak time points with HIV vaccine (ALVAC-HIV and AIDSVAX B/E)-induced responses. Four correlations were significant [false discovery rate-adjusted p-value (FDR) ≤ 0.2]. Three of these four were with IgG-binding antibody responses to TT measured one month after TT receipt, with the strongest and most significant correlation [rho = 0.368 (95% CI: 0.096, 0.588; p = 0.008; FDR = 0.137)] being with IgG-binding antibody responses to MN gp120 gDneg (B protein boost) measured two weeks after the second ALVAC-HIV and AIDSVAX B/E boost. The fourth significant correlation [(rho = 0.361; 95% CI: 0.049, 0.609; p = 0.021; FDR = 0.137)] was between CD4+ T-cell responses to a hepatitis B surface antigen peptide pool, measured 2 weeks after the third HBV vaccination, and IgG-binding antibody responses to gp70BCaseAV1V2 (B V1V2 immune correlate), measured two weeks after the second ALVAC-HIV and AIDSVAX B/E boost. These moderate correlations imply that either vaccine, TT or HBV, could potentially provide a moderately useful immunogenicity predictor for the ALVAC-HIV and AIDSVAX B/E HIV vaccine regimen.

Keywords: HIV vaccine; T-cell responses; binding antibodies; biomarkers; immune correlates.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • AIDS Vaccines* / administration & dosage
  • AIDS Vaccines* / immunology
  • Adult
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • CD4-Positive T-Lymphocytes* / immunology
  • Female
  • HIV Antibodies / blood
  • HIV Antibodies / immunology
  • HIV Infections* / immunology
  • HIV Infections* / prevention & control
  • HIV-1 / immunology
  • Hepatitis B Vaccines / administration & dosage
  • Hepatitis B Vaccines / immunology
  • Humans
  • Immunogenicity, Vaccine
  • Immunoglobulin G* / blood
  • Immunoglobulin G* / immunology
  • Male
  • Tetanus Toxoid / administration & dosage
  • Tetanus Toxoid / immunology
  • Viral Vaccines
  • Young Adult

Substances

  • AIDS Vaccines
  • Immunoglobulin G
  • Tetanus Toxoid
  • AIDSVAX B-E
  • HIV Antibodies
  • Hepatitis B Vaccines
  • ALVAC vaccine
  • AIDSVAX
  • Antibodies, Viral
  • Viral Vaccines