Lower viral loads and slower CD4 decline in MRKAd5 HIV-1 vaccinees expressing disease-susceptible HLA-B*58:02
| Autor: | Leitman, E, Hurst, J, Mori, M, Kublin, J, Ndung'u, T, Walker, B, Carlson, J, Gray, G, Matthews, P, Frahm, N, Goulder, P |
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| Rok vydání: | 2016 |
| Zdroj: | Journal of Infectious Diseases. 214(3) |
| ISSN: | 1537-6613 0022-1899 |
| Popis: | Background. HLA strongly influences HIV-1 disease progression. A major contributory mechanism is via the particular HLA-presented HIV-1 epitopes that are recognized by CD8+ T-cells. Different populations vary considerably in the HLA alleles expressed. We investigated the HLA-specific impact of the MRKAd5 HIV-1 Gag/Pol/Nef vaccine in a subset of the infected Phambili cohort in whom the disease-susceptible HLA-B*58:02 is highly prevalent. Methods. Viral loads, CD4 counts and ELISPOT anti-HIV-1 CD8+ T-cell responses for a subset of infected ART-naïve Phambili participants, selected according to sample availability, were analyzed. Results. Among those expressing disease-susceptible HLA-B*58:02, vaccinees had a lower chronic viral setpoint than placebo-recipients (median 7,240 versus 122,500 copies/ml, p=0.01), a 0.76log10 lower longitudinal viremia (p=0.01), and slower progression to CD4andLT;350 cells/mm3 (p=0.02). These differences were accompanied by higher Gag-specific breadth (4.5 versus 1 responses, p=0.04) and magnitude (2,300 versus 70 SFC/106 PBMC, p=0.06) in vaccinees versus placebo-recipients. Conclusions. In addition to the known enhancement of HIV-1 acquisition resulting from the MRKAd5 HIV-1 vaccine, these findings in a non-randomized subset of enrolees show an HLA-specific vaccine effect on time to CD4 decline and viremia post-infection and the potential for vaccines to differentially alter disease outcome according to population HLA composition. (Registration: NCT00413725, DOH-27-0207-1539.) |
| Databáze: | OpenAIRE |
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