A new study led by researchers from the U.S. Military HIV Research Program (MHRP) at the Walter Reed Army Institute of Research identified a transcriptional signature in B cells associated with protection from SIV or HIV infection in five independent trials of HIV-1 vaccine candidates. The gene expression signature was found to correlate with protection in the only human HIV vaccine trial that previously showed modest efficacy, RV144.
With results published in Science Translational Medicine, this signature and specific genes were previously shown to be induced in response to influenza and yellow fever vaccination in humans.
This study examined RNA-Seq data from preclinical HIV-1 vaccine candidate trials. The investigators proposed that partial efficacy observed in those studies could be due to variations in host gene expression elicited by the investigational vaccines. The team for the first time used a method called RNA-Seq and observed a common protective gene signature in the non-human primates.
Thereafter, the U.S. military scientists investigated whether or not this B-cell signature was associated with protection from HIV infection in the only clinical human HIV vaccine study to show modest efficacy: the RV144 trial conducted by MHRP and its partners in Thailand. RVV144 used a completely different vaccine Pox-protein regimen than what was used in the non-human primate studies.
They found that the B cell signature that correlated with protection in the preclinical studies also correlated with protection in the RV144 human vaccine efficacy trial, and in two additional Pox-protein vaccines in NH.
The B cell signature also associated with higher levels of a functional antiviral antibody response called antibody-dependent cellular phagocytosis, or ADCP that could shed some light on why the vaccine was protective.
Clinical Investigator Comments
Dr. Rasmi Thomas, MHRP Chief of Host Genomics noted: “We think this B cell signature is a broad indicator of effective responses after vaccination and could potentially be used to help design effective vaccines against HIV and other pathogens.” Thomas elaborated that the RNA-sequencing (RNA-seq) methods used int his study could prove to be a valuable tool to discover protective correlates in other clinical and preclinical trial. Thomas continued “We’re excited because the identified gene signature associate with protective efficacy for the two vaccine regimens that are currently being tested in human efficacy trials in Africa—the Imbokodo Study.”
Clinical Research Site
The U.S. Military HIV Research Program (MHRP) is at the forefront of the battle against HIV to protect U.S. troops from infection and to reduce the global impact of the disease. With an international network of research sites throughout Africa and Asia, the program’s growth and success has been achieved through a combination of strong science, careful development of research sites and partnerships with key research institutions in the U.S. and host countries.
Since its inception in 1986, MHRP has emerged as a world leader in HIV vaccine research, threat assessment, and epidemiology, HIV diagnostics and remission research. The integration of prevention and treatment has helped MHRP build strong and trusting relationships within the communities where research is conducted and provides an ethical framework to conduct HIV clinical research. MHRP is centered at the Walter Reed Army Institute of Research (WRAIR), U.S. Army Medical Research and Materiel Command.
Dr. Rasmi Thomas, MHRP Chief of Host Genomics
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