ATLANTA - Researchers at the Yerkes National Primate Research Center and the 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 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.
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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.
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.
Dedicated to discovering causes, preventions, treatments and cures, the Yerkes National Primate Research Center (NPRC), part of Emory University's Robert W. Woodruff Health Sciences Center, is fighting diseases and improving human health and lives worldwide. The center, one of only seven NPRCs the National Institutes of Health (NIH) funds, is supported by more than $74 million in research funding (all sources, fiscal year 2019). Yerkes researchers are making landmark discoveries in microbiology and immunology; neurologic diseases; neuropharmacology; behavioral, cognitive, and developmental neuroscience; and psychiatric disorders. Since 1984, the center has been fully accredited by the AAALAC International, regarded as the gold seal of approval for laboratory animal care. For more information about Yerkes and the seven NPRCs, visit NPRC.org and follow us at @NPRCnews.
The Emory Vaccine Center mission is to improve human health by conducting fundamental and clinical research that leads to the development of effective vaccines against diseases of global importance.
Journal
Science Immunology