1. Adenovirus-based HIV-1 vaccine candidates tested in efficacy trials elicit CD8+ T cells with limited breadth of HIV-1 inhibition.
- Author
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Hayes PJ, Cox JH, Coleman AR, Fernandez N, Bergin PJ, Kopycinski JT, Nitayaphan S, Pitisuttihum P, de Souza M, Duerr A, Morgan C, and Gilmour JW
- Subjects
- AIDS Vaccines administration & dosage, AIDS Vaccines genetics, CD4-Positive T-Lymphocytes virology, Cells, Cultured, Enzyme-Linked Immunospot Assay, Healthy Volunteers, Humans, Interferon-gamma metabolism, Vaccines, Synthetic administration & dosage, Vaccines, Synthetic genetics, Vaccines, Synthetic immunology, AIDS Vaccines immunology, Adenoviruses, Human genetics, CD8-Positive T-Lymphocytes immunology, Drug Carriers, HIV Infections prevention & control, HIV Infections therapy, HIV-1 immunology
- Abstract
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.
- Published
- 2016
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