A yeast-expressed RBD-based SARS-CoV-2 vaccine formulated with 3M-052-alum adjuvant promotes protective efficacy in non-human primates
María Pino, Talha Abid, Susan Pereira Ribeiro, Venkata Viswanadh Edara, Katharine Floyd, Justin C. Smith, Muhammad Latif, Gabriela Pacheco Sánchez, Debashis Dutta, Shelly Wang, Sanjeev Gumber, Shannon G. M. Kirejczyk, Joyce Cohen, Rachelle L. Stammen, Sherrie Jean, Jennifer Wood, Fawn Connor‐Stroud, Jeroen Pollet, Wen‐Hsiang Chen, Junfei Wei, Bin Zhan, Jungsoon Lee, Zhuyun Liu, Ulrich Strych, Neeta Shenvi, Kirk A. Easley, Daniela Weiskopf, Alessandro Sette, Justin Pollara, Dieter Mielke, Hongmei Gao, Nathan Eisel, Celia C. LeBranche, Xiaoying Shen, Guido Ferrari, Georgia D. Tomaras, David C. Montefiori, Rafick‐Pierre Sékaly, Thomas H. Vanderford, Mark A. Tomai, Christopher B. Fox, Mehul S. Suthar, Pamela A. Kozlowski, Peter J. Hotez, Mirko Paiardini, María Elena Bottazzi, Sudhir Pai Kasturi
Abstract
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.