Frederick National Laboratory develops new tools for HIV research
Scientists at the Frederick National Laboratory for Cancer Research (operated by Leidos Biomedical Research, Inc.), the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center, and a team of collaborators have filled a gap in HIV research by developing 38 new simian/human immunodeficiency viruses (SHIVs) for prevention and treatment studies. The viruses are available to the scientific community through the national laboratory’s AIDS and Cancer Virus Program (ACVP).
SHIVs are laboratory-engineered pathogens used to investigate HIV progression and evaluate potential new therapies and vaccines in certain laboratory models of the disease. According to the team’s paper in PLOS Pathogens, the new SHIVs differ from many existing ones in several beneficial ways.
Unlike most SHIVs, the new viruses model HIV subtype C, the most prevalent HIV subtype, which causes nearly half of HIV transmissions worldwide. Subtype C is especially prevalent in southern Africa and India. Consequently, these new SHIVs allow scientists to better investigate potential new HIV prevention strategies for people living in resource-limited areas.
Although other subtype-C SHIVs exist, their applicability in research is somewhat limited. For instance, many are created using HIV obtained from patients long after they acquired the virus. But because HIV mutates over time, those SHIVs don’t always resemble the circulating HIV involved in new transmissions. That in turn compromises prevention and treatment studies—if a vaccine is effective against a SHIV based on a mutated HIV, it may not work against the circulating infectious HIV.
Therefore, the team created its SHIVs using HIV from people who had recently acquired HIV and were participating in the Centre for the AIDS Programme of Research in South Africa cohort. These new viruses better model the circulating infectious forms of HIV subtype C, and pre-clinical studies have a better chance of predicting a vaccine’s effectiveness in those areas.
“Time is of the essence. The virus is adapting in populations, and having these models to test interventions is important,” said study author Brandon Keele, Ph.D., senior principal investigator, head of the Retroviral Evolution Section, and associate director of Research Support Cores in the ACVP.
The team also partially overcame another limitation facing traditional SHIVs—slow viral replication and spread inside the host—by introducing mutations into the new SHIVs. The mutations changed the SHIVs’ HIV sections enough to make the viruses spread more aggressively, like natural HIV, but not enough to compromise their integrity for prevention and treatment studies. The technique didn’t solve all the replication issues, but Keele said that the ACVP is “working diligently” on a better method.
The ACVP created the SHIVs to assist HIV prevention studies at NIAID’s Vaccine Research Center, and the paper and new viruses are just the latest example of a long-standing partnership between the two groups.
“Research takes a lot of effort, both time and money, so focusing on something that I think would be most relevant to treatment is what intrigued me with this project,” said Sean O'Brien, Ph.D., the molecular biologist and study author who engineered the viruses.
Scientists who wish to discuss or obtain the SHIVs for their research should contact Keele via the Retroviral Evolution Section web page. The SHIVs are available at no cost.
“We have the capacity to share hundreds of vials [with researchers who need them],” Keele said.