A Yeast Expressed RBD-Based SARS-CoV-2 Vaccine Formulated With 3M-052-Alum Adjuvant Promotes Protective Efficacy in Non-Human Primates
Ongoing 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 adjuvants. The RBD+3M-052-alum adjuvanted vaccine promoted better RBD binding and effector antibodies, higher CoV-2 neutralizing antibodies, improved Th1 biased CD4+T cell reactions, and increased CD8+ T cell responses when compared to the alum-alone adjuvanted vaccine. RBD+3M-052-alum induced a significant reduction of SARS-CoV-2 virus in 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 BAL. RBD+3M-052-alum blocked a post SARS-CoV-2 challenge increase in CD14+CD16++ intermediate blood monocytes, and Fractalkine, MCP-1, and TRAIL in the plasma. Decreased plasma analytes and intermediate monocyte frequencies correlated with reduced nasal and BAL viral loads. Lastly, 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.
American Association for the Advancement of Science [Society Publisher]
Pino, Maria; Abid, Talha; Ribeiro, Susan Pereira; Edara, Venkata Viswanadh; Floyd, Katharine; Smith, Justin C.; Latif, Muhammad Bilal; Pacheco-Sanchez, Gabriela; Dutta, Debashis; Wang, Shelly; Gumber, Sanjeev; Kirejczyk, Shannon; Cohen, Joyce; Stammen, Rachelle L.; Jean, Sherrie M.; Wood, Jennifer S.; Connor-Stroud, Fawn; Pollet, Jeroen; Chen, Wen Hsiang; Wei, Junfei; Zhan, Bin; Lee, Jungsoon; Liu, Zhuyun; Strych, Ulrich; Shenvi, Neeta; Easley, Kirk; Weiskopf, Daniela; and Sette, Alesandro, "A Yeast Expressed RBD-Based SARS-CoV-2 Vaccine Formulated With 3M-052-Alum Adjuvant Promotes Protective Efficacy in Non-Human Primates" (2021). School of Graduate Studies Faculty Publications. 26.