A yeast expressed RBD-based SARS-CoV-2 vaccineformulated with 3M-052-alum adjuvant promotesprotective efficacy in non-human primates

摘要

Ongoing SARS-CoV-2 vaccine development is focused on identifying stable, cost-effective, and accessiblecandidates for global use, specifically in low and middle-income countries. Here, we report the efficacy of arapidly scalable, novel yeast expressed SARS-CoV-2 specific receptor-binding domain (RBD) based vaccinein rhesus macaques. We formulated the RBD immunogen in alum, a licensed and an emerging alumadsorbed TLR-7/8 targeted, 3M-052-alum adjuvants. The RBD+3M-052-alum adjuvanted vaccine promotedbetter RBD binding and effector antibodies, higher CoV-2 neutralizing antibodies, improved Th1 biasedCD4+T cell reactions, and increased CD8+ T cell responses when compared to the alum-alone adjuvantedvaccine. RBD+3M-052-alum induced a significant reduction of SARS-CoV-2 virus in respiratory tract uponchallenge, accompanied by reduced lung inflammation when compared with unvaccinated controls. AntiRBD antibody responses in vaccinated animals inversely correlated with viral load in nasal secretions andBAL. RBD+3M-052-alum blocked a post SARS-CoV-2 challenge increase in CD14+CD16++ intermediateblood monocytes, and Fractalkine, MCP-1, and TRAIL in the plasma. Decreased plasma analytes andintermediate monocyte frequencies correlated with reduced nasal and BAL viral loads. Lastly, RBD-specificplasma cells accumulated in the draining lymph nodes and not in the bone marrow, contrary to previousfindings. Together, these data show that a yeast expressed, RBD-based vaccine+3M-052-alum providesrobust immune responses and protection against SARS-CoV-2, making it a strong and scalable vaccinecandidate.