Novel adjuvant helps extend immunity against HIV in primates

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Researchers at the Yerkes National Primate Research Center and the Emory Vaccine Center (EVC) (both GA, USA) have demonstrated that a novel adjuvant termed 3M-052 can extend immunity against HIV in rhesus monkeys. The results of the study, published in Science Immunology, could have implications for the development of successful vaccines against HIV, influenza and COVID-19.

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“We have known adjuvants are critical immunity-boosting supplements that help improve the effectiveness of vaccines,” commented Sudhir Pai Kasturi (Emory University), first author of the study. “Until now, however, it has been unclear which class of adjuvants can promote stable and long-lived immunity in nonhuman primate models.”

While vaccines are capable of eliciting short-term responses, the durability of antibody responses depend on both the antigen produced and the adjuvants used in the vaccine

In an effort to advance prolong the immunizing effects of HIV vaccines, the team of researchers conducted a pre-clinical study of 90 rhesus macaques examining their immune response to the adjuvant 3M-052, a TLR7/8 agonist. This involved using a nanoparticle and a clinically applicable alum adsorbed formulation of 3M-052.

The researchers observed sustained antibody responses to an HIV-1 envelope (Env) protein vaccine, with the adjuvant inducing vaccine-specific, long-lived bone marrow plasma cells (BM-LLPCs), which are critical for durable immunity. These cells we maintained at high numbers for more than 1 year post-vaccination.

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This prolonged interval is both indicative of pre-clinical efficacy and potentially informative in selecting vaccine candidates.

“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,” explained Rafi Ahmed (Emory Vaccine Center), co-senior author. “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 results of the study have already prompted a Phase I clinical trial to assess the potential of 3M-052 in the context of HIV Env antigens.

Sources: Kasturi SP, Rasheed MAU, Havenar-Daughton C et al. 3M-052, a synthetic TLR-7/8 agonist, induces durable HIV-1 envelope–specific plasma cells and humoral immunity in nonhuman primates. Sci. Immunol. doi: 10.1126/sciimmunol.abb1025 (2020); www.yerkes.emory.edu/about/news/microbiology_immunology/Kasturi_New_Adjuvant_Extends_HIV_Immunity.html

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