An AIDS vaccine tested in people, but found to be ineffective, influenced the genetic makeup of the virus that slipped past. The findings suggest new ideas for developing HIV vaccines.
The results were published Feb. 27 in Nature Medicine.
This is the first evidence that vaccine-induced cellular immune responses against HIV-1 infection exert selective pressure on the virus. "Selective pressure" refers to environmental demands that favor certain genetic traits over others.
The senior author of the multi-institutional study is Dr. James I. Mullins, University of Washington (UW) professor of microbiology. The research team analyzed the genome sequences in HIV-1 isolated from 68 newly infected volunteers in the STEP HIV-1 vaccine trial. Mullins and the other principal researchers who carried out this study were not involved in the STEP trial.
The STEP trial was a double-blind, Phase 2B test-of-concept of a Merck HIV-1 subtype B vaccine. The vaccine, MRKAd5, was designed to make the body produce infection-fighting white blood cells, commonly called killer T-cells, that could recognize and target specific parts of HIV-1 known as Gag, Pol and Nef.
The STEP trial was conducted at 34 North American, Caribbean, South American and Australian locations where the HIV-1 subtype B was the predominant virus in the local HIV-infected populations. The trial enrolled 3,000 participants.
Preliminary tests indicated the vaccine was encouraging the appearance of the desired virus-attacking cells. More than 75 percent of vaccinated participants produced HIV-1 specific T cells.
Nevertheless, this response to the vaccine did not predict protection. The trial failed. Immunizations were halted, Mullins recalled, after the first interim analysis indicated that the vaccine neither prevented HIV-1 infection nor reduced the load of virus in the body.
"Even though the T-cell responses were not sufficient to
|Contact: Leila Gray|
University of Washington