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

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.

• Authors: Maria Pino, Talha Abid, Susan Pereira Ribeiro, Venkata Viswanadh Edara, Katharine Floyd, Justin C Smith, Muhammad Bilal Latif, Gabriela Pacheco-Sanchez, Debashis Dutta, Shelly Wang, Sanjeev Gumber, Shannon Kirejczyk, Joyce Cohen, Rachelle L Stammen, Sherrie M Jean, Jennifer S Wood, Fawn Connor-Stroud, Jeroen Pollet, Wen-Hsiang Chen, Junfei Wei, Bin Zhan, Jungsoon Lee, Zhuyun Liu, Ulrich Strych, Neeta Shenvi, Kirk Easley, Daniela Weiskopf, Alessandro Sette, Justin Pollara, Dieter Mielke, Hongmei Gao, Nathan Eisel, Celia C LaBranche, Xiaoying Shen, Guido Ferrari, Georgia D Tomaras, David C Montefiori, Rafick P Sekaly, Thomas H Vanderford, Mark A Tomai, Christopher B Fox, Mehul S Suthar, Pamela A Kozlowski, Peter J Hotez, Mirko Paiardini, Maria Elena Bottazzi, Sudhir Pai Kasturi
• Journal: Science immunology (Sci Immunol) Vol. 6 Issue 61 (07 15 2021) ISSN: 2470-9468 [Electronic] United States
• PMID: 34266981 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright A(c) 2021, American Association for the Advancement of Science.

Chemical References

• Adjuvants, Immunologic
• Alum Compounds
• Antibodies, Neutralizing
• Antibodies, Viral
• COVID-19 Vaccines
• Cytokines
• Immunoglobulin G
• Spike Glycoprotein, Coronavirus
• aluminum sulfate

Topics

• Adjuvants, Immunologic (administration & dosage)
• Administration, Inhalation
• Administration, Intranasal
• Alum Compounds (administration & dosage)
• Animals
• Antibodies, Neutralizing (immunology)
• Antibodies, Viral (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• COVID-19 (immunology, pathology, prevention & control, virology)
• COVID-19 Vaccines
• Cell Line
• Cytokines (immunology)
• Humans
• Immunoglobulin G (immunology)
• Lung (pathology)
• Macaca mulatta
• Male
• Protein Binding
• Protein Domains
• SARS-CoV-2
• Saccharomycetales (genetics)
• Spike Glycoprotein, Coronavirus (genetics, immunology)
• Viral Load