Adenovirus-based HIV-1 vaccine candidates tested in efficacy trials elicit CD8+ T cells with limited breadth of HIV-1 inhibition

AIDS. 2016 Jul 17;30(11):1703-12. doi: 10.1097/QAD.0000000000001122.


Objectives: The ability of HIV-1 vaccine candidates MRKAd5, VRC DNA/Ad5 and ALVAC/AIDSVAX to elicit CD8 T cells with direct antiviral function was assessed and compared with HIV-1-infected volunteers.

Design: Adenovirus serotype 5 (Ad5)-based regimens MRKAd5 and VRC DNA/Ad5, designed to elicit HIV-1-specific T cells, are immunogenic but failed to prevent infection or impact on viral loads in volunteers infected subsequently. Failure may be due in part to a lack of CD8 T cells with effective antiviral functions.

Methods: An in-vitro viral inhibition assay tested the ability of bispecific antibody expanded CD8 T cells from peripheral blood mononuclear cells to inhibit replication of a multiclade panel of HIV-1 isolates in autologous CD4 T cells. HIV-1 proteins recognized by CD8 T cells were assessed by IFNγ enzyme-linked immunospot assay.

Results: Ad5-based regimens elicited CD8 T cells that inhibited replication of HIV-1 IIIB isolate with more limited inhibition of other isolates. IIIB isolate Gag and Pol genes have high sequence identities (>96%) to vector HIV-1 gene inserts, and these were the predominant HIV-1 proteins recognized by CD8 T cells. Virus inhibition breadth was greater in antiretroviral naïve HIV-1-infected volunteers naturally controlling viremia (plasma viral load < 10 000/ml). HIV-1-inhibitory CD8 T cells were not elicited by the ALVAC/AIDSVAX regimen.

Conclusion: The Ad5-based regimens, although immunogenic, elicited CD8 T cells with limited HIV-1-inhibition breadth. Effective T-cell-based vaccines should presumably elicit broader HIV-1-inhibition profiles. The viral inhibition assay can be used in vaccine design and to prioritize promising candidates with greater inhibition breadth for further clinical trials.

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology*
  • Adenoviruses, Human / genetics*
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Drug Carriers*
  • Enzyme-Linked Immunospot Assay
  • HIV Infections / prevention & control*
  • HIV Infections / therapy*
  • HIV-1 / immunology*
  • Healthy Volunteers
  • Humans
  • Interferon-gamma / metabolism
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology


  • AIDS Vaccines
  • Drug Carriers
  • Vaccines, Synthetic
  • Interferon-gamma