A modular protein subunit vaccine candidate produced in yeast confers protection against SARS-CoV-2 in non-human primates
| Autor: | Sangeeta B. Joshi, Jingyou Yu, Lisa H. Tostanoski, Christopher A Naranjo, Amanda J. Martinot, J. Christopher Love, Sumi Biswas, Jason Velasco, Judith M. Silverman, Harry Kleanthous, Neil C. Dalvie, Elyse Teow, Kawaljit Kaur, Felix Nampanya, Dongsoo Yun, Sergio A. Rodriguez-Aponte, Shivani A. Patel, David B. Volkin, Sakshi Bajoria, Lesley Bowman, Anthony L. Cook, Mark G. Lewis, Aiquan Chang, Dan H. Barouch, Abishek Chandrashekar, Ozan S. Kumru, Danielle L Camp, Zach Flinchbaugh, Renita Brown, Katherine McMahan, Laurent Pessaint, Hanne Leth Andersen, Noe B. Mercado, Victoria M. Giffin |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | bioRxiv article-version (status) pre article-version (number) 1 |
| DOI: | 10.1101/2021.07.13.452251 |
| Popis: | Vaccines against SARS-CoV-2 have been distributed at massive scale in developed countries, and have been effective at preventing COVID-19. Access to vaccines is limited, however, in low- and middle-income countries (LMICs) due to insufficient supply, high costs, and cold storage requirements. New vaccines that can be produced in existing manufacturing facilities in LMICs, can be manufactured at low cost, and use widely available, proven, safe adjuvants like alum, would improve global immunity against SARS-CoV-2. One such protein subunit vaccine is produced by the Serum Institute of India Pvt. Ltd. and is currently in clinical testing. Two protein components, the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen virus-like particles (VLPs), are each produced in yeast, which would enable a low-cost, high-volume manufacturing process. Here, we describe the design and preclinical testing of the RBD-VLP vaccine in cynomolgus macaques. We observed titers of neutralizing antibodies (>104) above the range of protection for other licensed vaccines in non-human primates. Interestingly, addition of a second adjuvant (CpG1018) appeared to improve the cellular response while reducing the humoral response. We challenged animals with SARS-CoV-2, and observed a ~3.4 and ~2.9 log10reduction in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, compared to sham controls. These results inform the design and formulation of current clinical COVID-19 vaccine candidates like the one described here, and future designs of RBD-based vaccines against variants of SARS-CoV-2 or other betacoronaviruses. |
| Databáze: | OpenAIRE |
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