MHRP’s molecular epidemiologists played a key role on a research team that analyzed the HIV-1 genome sequences from infected volunteers in the Step HIV vaccine trial.
MHRP’s molecular epidemiologists played a key role on a research team that analyzed the HIV-1 genome sequences from infected volunteers in the Step HIV vaccine trial. Findings indicate that that although ineffective at preventing infection, the vaccine impacted the genetic makeup of the virus that infected the volunteers. Results were published Feb. 27 in Nature Medicine.
After comparing the genetic strains of HIV in vaccine and placebo recipients, researchers found that cellular immune responses generated by the vaccine may have impacted the HIV-1 strains that established infections (breakthrough viruses).
Researchers isolated and then analyzed the HIV-1 whole genome sequences from 68 newly infected volunteers in the Step study. Findings showed subtle differences between the viral genetic sequences taken from the vaccinated individuals, compared to the placebo recipients. The differences occurred only in the sequences for the proteins targeted by the HIV vaccine.
“Although the vaccine used in the Step trial failed to show efficacy, it is interesting to see that the vaccine had an impact on the HIV-1 strains that established infections in vaccines," said lead author Morgan Rolland, Ph.D. “Finding that cellular immune responses elicited by the vaccine left genetic hallmarks on the founder viruses is important because it can help us devise better antigen candidates to include in future vaccines designed to elicit cellular immunity.” Dr. Rolland was a member of the research team at the University of Washington at the time of this study and is currently a scientist at MHRP.
MHRP and its collaborators are conducting similar studies on the genetic impact of RV144. These results may provide new ways for vaccine researchers to target HIV and may influence the design of future HIV vaccines.
The Step study, an international HIV vaccine trial co-sponsored by the National Institute of Allergy and Infectious Diseases and the pharmaceutical company Merck, was halted in 2007 when the vaccine failed to prevent HIV infection in volunteers or affect the virus load in those infected.