Vaccines are designed to induce a robust immune response, typically via antibodies and T cells, that protects against infection. A person’s genetic makeup can have a sizeable impact on vaccine efficacy through genes called HLA. Some HLA alleles promote strong T-cell responses to a given antigen (e.g., the HIV protein Gag), whereas others may have no effect at all. The Step HIV vaccine phase IIb clinical trial, the first of its kind designed to elicit T-cell responses, was prematurely halted due to an increased risk of infection in Ad5 seropositive, uncircumcised men. After termination of the Step trial, scientists wondered whether some immune responses to the vaccine might affect post HIV infection outcome.
Using data obtained from Step, Associate Member of VIDD Dr. Holly Janes, along with VIDD Members Drs. Daniel Geraghty, Peter Gilbert and Julie McElrath and Associate Member Dr. Nicole Frahm, examined the relationship between vaccine-induced T-cell responses to Gag and plasma viral load, as well as possible correlations to HLA allele expression. They used samples from a total of 154 study subjects who acquired HIV during the trial: 95 vaccine and 59 placebo recipients. The authors grouped subjects according to the number of Gag responses (0, 1-2 and >2) and looked for an association with viral load. They found that T-cell responses targeting multiple Gag epitopes were associated with lower viral load in vaccinated recipients. Specifically, persons targeting more than two Gag epitopes had over a 5 times lower viral load than those not targeting Gag at all. Lessened viremia was also associated with expression of HLA alleles B*27, B*57 and B*58:01, which have been implicated in better disease outcome in unvaccinated HIV-infected indivuduals, presumably due to the binding predilection to epitopes in conserved regions of Gag. Vaccines containing Gag epitopes presented by these HLA alleles that stimulate multiple T-cell responses could theoretically be capable of controlling HIV disease progression.
Janes H, Friedrich DP, Krambrink A, Smith RJ, Kallas EG, Horton H, Casimiro DR, Carrington M, Geraghty DE, Gilbert PB, McElrath MJ, Frahm N. Vaccine-induced gag-specific T cells are associated with reduced viremia after HIV-1 infection. J Infect Dis. 2013 Oct 15;208(8):1231-9. doi: 10.1093/infdis/jit322. Epub 2013 Jul 21.