Adjuvanting RBD-NP with a STING agonist/alum induces potent viral neutralizing antibody titers in non-human primates 3793

Abstract Description The development of vaccines reduced the prevalence of infectious diseases from smallpox to COVID-19; however, despite this astounding success, certain pathogens evade the immune response leading to break through infections. Breakthrough infections highlight the need to improve vaccine induced immune activation to prevent infectious disease. The Stimulator of Interferon Genes (STING) pathway senses dsDNA and has been targeted in immune stimulating cancer therapies. However, in the context of infectious diseases, STING agonists have not been investigated as vaccine adjuvants. Therefore, we vaccinated rhesus macaques with SARS CoV2 Receptor Binding Domain (RBD) nanoparticle (NP) adjuvanted with a small molecule STING agonist formulated with alum on days 0 and 21 and analyzed the humoral and cellular immune responses, as well as systemic cytokine levels. Strikingly, we found that despite the modest RBD binding antibody titers there was a robust neutralizing antibody response induced by RBD-NP + STING agonist/alum. In addition, RBD NP adjuvanted with STING agonist/alum induced an RBD specific TH1 CD4+ T cell response. Analysis of systemic cytokine levels in the serum demonstrated elevated IP10 levels 1 day after prime and boost. These findings highlight that using a STING agonist as a vaccine adjuvant to induce potent neutralizing antibody titers. Funding Sources Bill and Melinda Gates Foundation Discovery Hub Topic Categories Vaccines and Immunotherapy (VAC)