Researchers at Emory University’s Yerkes National Primate Research Center and Emory Vaccine Center (EVC) are first to show a new adjuvant, 3M-052, helps induce long-lasting immunity against HIV. The study results are published today in Science Immunology.
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 Emory School of Medicine 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.
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.
This study was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health. Grant amounts (direct + indirect) are:
Bill and Melinda Gates Foundation: $2,738,195/over 3 years; and #OPP1055855, $9,778,596/over 3 years
NIH K01 OD023039-03, $346,266/yr; 8/8/16 – 7/31/20
NIH R01 AI125068, $841,574/yr; 2/1/16 – 1/31/21
NIH P30 AI050409, $2,249,998/yr; 8/1/17-7/31/22
NIH P51 OD011132, $10,540,602/yr
Note: Some amounts listed are for the full grants; only a portion of the grant funding was applied to the study reported in this news release.