A yeast-expressed RBD-based SARS-CoV-2 vaccine formulated with 3M-052-alum adjuvant promotes protective efficacy in non-human primates

Ongoing severe acute respiratory syndrome coronavirus–2 (SARS-CoV-2) vaccine development is focused on identifying stable, cost-effective, and accessible candidates for global use, specifically in low- and middle-income countries. Here, we report the efficacy of a rapidly scalable, novel yeast-expressed SARS-CoV-2–specific receptor binding domain (RBD)–based vaccine in rhesus macaques. We formulated the RBD immunogen in alum, a licensed and an emerging alum-adsorbed TLR-7/8-targeted, 3M-052-alum adjuvant. The RBD + 3M-052-alum–adjuvanted vaccine promoted better RBD binding and effector antibodies, higher CoV-2 neutralizing antibodies, improved T(H)1-biased CD4(+) T cell reactions, and increased CD8(+) T cell responses when compared with the alum-alone adjuvanted vaccine. RBD + 3M-052-alum induced a significant reduction of SARS-CoV-2 virus in the respiratory tract upon challenge, accompanied by reduced lung inflammation when compared with unvaccinated controls. Anti-RBD antibody responses in vaccinated animals inversely correlated with viral load in nasal secretions and bronchoalveolar lavage (BAL). RBD + 3M-052-alum blocked a post–SARS-CoV-2 challenge increase in CD14(+)CD16(++) intermediate blood monocytes, and fractalkine, MCP-1 (monocyte chemotactic protein–1), and TRAIL (tumor necrosis factor–related apoptosis-inducing ligand) in the plasma. Decreased plasma analytes and intermediate monocyte frequencies correlated with reduced nasal and BAL viral loads. Last, RBD-specific plasma cells accumulated in the draining lymph nodes and not in the bone marrow, contrary to previous findings. Together, these data show that a yeast-expressed, RBD-based vaccine + 3M-052-alum provides robust immune responses and protection against SARS-CoV-2, making it a strong and scalable vaccine candidate.