A yeast expressed RBD-based SARS-CoV-2 vaccine formulated with 3M-052-alum adjuvant promotes protective efficacy in non-human primates
| Autor: | Guido Ferrari, Neeta Shenvi, Thomas H. Vanderford, Susan Pereira Ribeiro, Wen-Hsiang Chen, David C. Montefiori, Talha Abid, Alessandro Sette, Daniela Weiskopf, Debashis Dutta, Katharine Floyd, Shelly Wang, Dieter Mielke, Sudhir Pai Kasturi, Georgia D. Tomaras, Pamela A. Kozlowski, Celia C. LaBranche, Maria Pino, Jungsoon Lee, Sherrie Jean, Venkata Viswanadh Edara, Xiaoying Shen, Justin Pollara, Justin C Smith, Mirko Paiardini, Rafick Pierre Sekaly, Fawn Connor-Stroud, Joyce Cohen, Gabriela Pacheco-Sanchez, Hongmei Gao, Zhuyun Liu, Christopher B. Fox, Sanjeev Gumber, Junfei Wei, Nathan Eisel, Maria Elena Bottazzi, Rachelle L. Stammen, Jennifer S. Wood, Shannon Kirejczyk, Bin Zhan, Muhammad Bilal Latif, Peter J. Hotez, Kirk Easley, Ulrich Strych, Jeroen Pollet, Mehul S. Suthar, Mark A. Tomai |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Male Immunogen COVID-19 Vaccines T cell Immunology Biology CD8-Positive T-Lymphocytes Antibodies Viral Immunoglobulin G Cell Line 03 medical and health sciences 0302 clinical medicine Immune system Adjuvants Immunologic Protein Domains Administration Inhalation medicine Animals Humans Alum adjuvant Lung Administration Intranasal SARS-CoV-2 COVID-19 General Medicine Viral Load Antibodies Neutralizing Macaca mulatta 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Saccharomycetales Spike Glycoprotein Coronavirus biology.protein Alum Compounds Cytokines Nasal administration Antibody Viral load Protein Binding |
| Zdroj: | Science immunology. 6(61) |
| ISSN: | 2470-9468 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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