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Outcomes of HIV Vaccine Related to Genetic Variation
September 15, 2015
Variations in the human leukocyte antigen (HLA) gene appear to be related to outcomes after receipt of an HIV vaccine that was previously shown to protect some individuals from the virus but not others, according to a study by researchers from the United States and Thailand (Prentice HA et al. Sci Transl Med. 2015;7:296ra112).
In 2009, a phase 3 clinical trial of the RV144 HIV-1 vaccine reported an estimated vaccine efficacy of 31.2% (Rerks-Ngarm S et al. N Engl J Med. 2009;361:2209-2220). In a follow-up study in 2012, researchers determined that 2 different antibody responses may explain why some vaccine recipients were protected and others were not: high levels of immunoglobulin G (IgG) antibodies specific to a region of the outer HIV envelope correlated with lower infection rates, while high levels of IgA antibodies specific to the HIV envelope were associated with increased risk of infection (Haynes BF et al. N Engl J Med. 2012;366:1275-1286).
Because previous studies suggested that genetic variations in HLA class II alleles have an important function in antibody responses to vaccination, researchers involved in this most recent study sought to determine whether such variation was related to HIV-specific antibody levels and HIV acquisition after RV144 vaccination in participants from the original 2009 trial.
The researchers found that high IgG antibody responses to the RV144 vaccine were associated with decreased risk of HIV-1 acquisition only in participants with the HLA DPB1*13 allele. In contrast, high IgA antibody responses were related to increased risk of HIV infection only in participants with the DQB1*06 allele, suggesting the protection associated with the vaccine may be negated in individuals with this HLA variant.
The authors suggest that “differences in vaccine-induced responses elicited by individuals with HLA-DPB1*13 should be further examined to determine the mechanism of protection of the vaccine.” A better understanding of this mechanism could help improve the design of an HIV vaccine.