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Sub-Saharan Africa and the Caribbean countries bear a disproportionate burden of the HIV pandemic. This suggests a genetic predisposition arising from a common ancestry. A 40% HIV risk-reduction associated with Rh2 blood group was reported in a previous study by the same authors. The current study seeks to elucidate potential mechanisms for this risk reduction. Lymphocyte sub-populations and viral load measurements were achieved by routine diagnostic laboratory methods in 102 untreated HIV-1 infected patients. The results were compared across the categories of RH2 blood group. Carriage of the Rh2 antigen was associated with a higher proportion of T-cells (82±8% versus 75±10%, P=0.001), especially single-positive (CD8+) cytotoxic T-cells (64±14 versus 54±13%, P=0.004). High absolute CD8 counts were more prevalent among the Rh2-positive than the Rh2-negative subjects (90% versus 65%, p=0.023). Among the Rh2-positive subjects, the increase in CD8 count paralleled the viral load in comparison to the Rh2-negatives (r²=0.630, P<0.0001 versus r2=0.148, P<0.001, respectively). The results suggest that Rh2 enhances the CD8 counts in an HIV infection, and its cells are known to play a vital role in immunity against HIV. This probably explains the protective role observed against HIV-1 infection. [ABSTRACT FROM AUTHOR]

Over 90% of HIV/AIDS positive individuals in sub-Saharan Africa are infected with highly heterogeneous HIV-1 subtype C (HIV-1C) viruses. One of the best ways to reduce the burden of this disease is the development of an affordable and effective prophylactic vaccine. Mosaic immunogens are computationally designed to overcome the hurdle of HIV diversity by maximizing the expression of potential T cell epitopes. Mycobacterium bovis BCG ΔpanCD auxotroph and modified vaccinia Ankara (MVA) vaccines expressing HIV-1C mosaic Gag (GagM) were tested in a prime-boost regimen to demonstrate immunogenicity in a mouse study. The BCG-GagM vaccine was stable and persisted 11.5 weeks post vaccination in BALB/c mice. Priming with BCG-GagM and boosting with MVA-GagM elicited higher Gag-specific IFN-γ ELISPOT responses than the BCG-GagM only and MVA-GagM only homologous vaccination regimens. The heterologous vaccination also generated a more balanced and persistent CD4+ and CD8+ T cell Gag-specific IFN-γ ELISPOT response with a predominant effector memory phenotype. A Th1 bias was induced by the vaccines as determined by the predominant secretion of IFN-γ, TNF-α, and IL-2. This study shows that a low dose of MVA (104 pfu) can effectively boost a BCG prime expressing the same mosaic immunogen, generating strong, cellular immune responses against Gag in mice. Our data warrants further evaluation in non-human primates. A low dose vaccine would be an advantage in the resource limited countries of sub-Saharan Africa and India (where the predominating virus is HIV-1 subtype C). [ABSTRACT FROM AUTHOR]