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.
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.
Authors: Daniel T Claiborne; Eileen P Scully; Christine D Palmer; Jessica L Prince; Gladys N Macharia; Jakub Kopycinski; Clive M Michelo; Howard W Wiener; Rachel Parker; Krystelle Nganou-Makamdop; Daniel Douek; Marcus Altfeld; Jill Gilmour; Matt A Price; Jianming Tang; William Kilembe; Susan A Allen; Eric Hunter Journal: PLoS Pathog Date: 2019-08-26 Impact factor: 6.823
Authors: Peter Hayes; Natalia Fernandez; Christina Ochsenbauer; Jama Dalel; Jonathan Hare; Deborah King; Lucas Black; Claire Streatfield; Vanaja Kakarla; Gladys Macharia; Julia Makinde; Matt Price; Eric Hunter; Jill Gilmour Journal: PLoS One Date: 2021-11-17 Impact factor: 3.240
Authors: Gaudensia Mutua; Bashir Farah; Robert Langat; Jackton Indangasi; Simon Ogola; Brian Onsembe; Jakub T Kopycinski; Peter Hayes; Nicola J Borthwick; Ambreen Ashraf; Len Dally; Burc Barin; Annika Tillander; Jill Gilmour; Jan De Bont; Alison Crook; Drew Hannaman; Josephine H Cox; Omu Anzala; Patricia E Fast; Marie Reilly; Kundai Chinyenze; Walter Jaoko; Tomáš Hanke; The Hiv-Core 004 Study Group Journal: Mol Ther Methods Clin Dev Date: 2016-08-31 Impact factor: 6.698