HIV Immunology: What Lessons Can We Learn from Recent Vaccine Trials?(Leading Article) (Human Immunodeficiency Virus) (Report‪)‬

Results from two large HIV vaccine studies, the STEP and RV144 trials, gave surprising and divergent results that have raised more questions than answers in efforts to understand the immunology of HIV-1 infection and to develop successful vaccines against this condition. The STEP trial was a double-blind Phase 2 study, in which 3000 high-risk healthy uninfected volunteers were randomly allocated to receive three injections of an adenovirus serotype 5 viral vector expressing three HIV-1 genes (gag, pol, nef) or placebo [1]. The aim of the study was to test the capacity of the vaccine to reduce acquisition of HIV-1 infection or to decrease viral load set-point in vaccinated individuals who subsequently had breakthrough infection. A major issue for this vaccine was the high prevalence of adenovirus-specific antibodies as a result of prior exposure to the virus, particularly in sub-Saharan Africa, which would have been expected to lead to reduced immunogenicity.