New adjuvant successful in extending immunity against HIV

In this pre-clinical study that included 90 rhesus monkeys, the researchers showed 3M-052, a new, synthetic small molecule that targets a specific receptor (TLR 7/8), successfully induced vaccine-specific, long-lived bone marrow plasma cells (BM-LLPCs), which are critical for durable immunity. In a striking observation, 3M-052-induced BM-LLPCs were maintained at high numbers for more than one year after vaccination. This prolonged interval is not only feasible in monitoring pre-clinical effectiveness, it is also highly informative in down selecting vaccine candidates.

First author Sudhir Pai Kasturi, PhD, an assistant professor in the Department of Pathology and Laboratory Medicine and a research assistant professor at Yerkes and the EVC, says, "We have known adjuvants are critical immunity-boosting supplements that help improve the effectiveness of vaccines. Until now, however, it has been unclear which class of adjuvants can promote stable and long-lived immunity in nonhuman primate models. Our study provides that information."

Co-senior author Rafi Ahmed, PhD, director of the Emory Vaccine Center, adds, "The key to a successful vaccine is durability of immune responses. Antibodies provide the first line of defense against pathogens, and antibody levels are maintained by the generation of long-lived plasma cells that reside in bone marrow. Our study identifies an adjuvant that is effective in generating such long-lived plasma cells in bone marrow. This finding has implications for developing successful vaccines against HIV, influenza and, especially important now, COVID-19.

The research data from this study has prompted a phase 1 clinical trial to assess the potential of 3M-052 in the context of HIV Env antigens; see http://clinicaltrials.gov NCT04177355.

Research collaborators include Bali Pulendran, PhD, senior author and a professor at Stanford; Mohammed Ata Ur Rasheed, PhD, co-first author and a researcher in Dr. Ahmed's lab at the time of the study and now with the CDC; Christopher Fox, PhD, Infectious Disease Research Institute, who prepared the clinical grade adjuvant formulation; and Mark Tomai, PhD, and his team at 3M Drug Delivery Systems in Minnesota, who discovered the novel 3M-052 adjuvant.