Vaccine and Infectious Disease Division

Sieving through Step trial data

The HVTN’s Step trial was halted in 2007 for the test vaccine’s failure to protect against HIV infection, but analyses of the large amounts of data continues to this day and HVTN and other researchers have made many fruitful discoveries about HIV infection and our immune reactions to the virus and vaccine. A 2011 analysis by VIDD researchers found that although the Step trial vaccine did not protect against HIV infection, the HIV sequences found among study participants who became infected despite receiving the vaccine differed from the sequences in the placebo group. That is, the vaccine exerted some kind of ‘sieve effect’ on infecting HIV viruses.

Now, VIDD associate member Dr. Holly Janes, along with colleagues including VIDD assistant member Dr. Nicole Frahm, senior research associate Alan DeCamp, postdoctoral fellow Dr. Erin Gabriel, staff scientist Dr. Tomer Hertz, co-director Dr. Julie McElrath, member Dr. Peter Gilbert and Center Director Dr. Larry Corey, looked at the immune responses to the vaccine inserts in those who became infected in the Step trial, to better understand how the vaccine elicited its sieve effect. The researchers found that CD8+ T cells, but not CD4+ T cells, showed a vaccine-specific response post-infection. There was some evidence of HIV sequence differences between infected vaccine and placebo recipients in regions targeted by vaccine-induced immune responses. However, the immune responses were not correlated with viral sequence measurements, either in terms of their magnitude or location within each vaccine insert protein. Therefore these responses do not fully explain the sieve effect. They also found that the vaccine may have had a weak effect on HIV viral load, suggesting that a more robust CD8+ T cell response may be an effective strategy to protect against HIV infection. – RT

Janes H, Frahm N, Decamp A, Rolland M, Gabriel E, Wolfson J, Hertz T, Kallas E, Goepfert P, Friedrich DP, Corey L, Mullins JI, McElrath MJ, Gilbert P. MRKAd5 HIV-1 Gag/Pol/Nef Vaccine-Induced T-Cell Responses Inadequately Predict Distance of Breakthrough HIV-1 Sequences to the Vaccine or Viral Load. PLoS One. 2012;7(8):e43396.