A modular protein subunit vaccine candidate produced in yeast confers protection against SARS-CoV-2 in non-human primates
A modular protein subunit vaccine candidate produced in yeast confers protection against SARS-CoV-2 in non-human primates
Abstract 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 log10 reduction 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.
Mercado Noe B.、Dalvie Neil C.、Kaur Kawaljit、McMahan Katherine、Yu Jingyou、Nampanya Felix、Brown Renita、Teow Elyse、Kleanthous Harry、Biswas Sumi、Martinot Amanda J.、Giffin Victoria M.、Yun Dongsoo、Chang Aiquan、Chandrashekar Abishek、Naranjo Christopher A.、Camp Danielle L.、Rodriguez-Aponte Sergio A、Love J. Christopher、Barouch Dan H.、Bajoria Sakshi、Pessaint Laurent、Velasco Jason、Patel Shivani、Bowman Lesley、Tostanoski Lisa H.、Silverman Judith Maxwell、Andersen Hanne、Volkin David B.、Cook Anthony、Joshi Sangeeta B.、Flinchbaugh Zach、Lewis Mark G.、Kumru Ozan S.
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical SchoolDepartment of Chemical Engineering, Massachusetts Institute of Technology||The Koch Institute for Integrative Cancer Research, Massachusetts Institute of TechnologyDepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of KansasCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical SchoolCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical SchoolCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical SchoolBioqualBioqualBill & Melinda Gates FoundationBill & Melinda Gates FoundationCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School||Departments of Infectious Diseases and Global Health and Comparative Pathobiology, Cummings School of Veterinary Medicine, Tufts UniversityCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical SchoolThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of TechnologyCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School||Harvard Medical SchoolCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical SchoolThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of TechnologyThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of TechnologyThe Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology||Department of Biological Engineering, Massachusetts Institute of TechnologyDepartment of Chemical Engineering, Massachusetts Institute of Technology||The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology||Ragon Institute of MGH, MITCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School||Harvard Medical School||Ragon Institute of MGH, MIT||Massachusetts Consortium on Pathogen ReadinessDepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of KansasBioqualBioqualCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical SchoolSpyBiotech Limited, Oxford Business Park NorthCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical SchoolBill & Melinda Gates Medical Research InstituteBioqualDepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of KansasBioqualDepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of KansasBioqualBioqualDepartment of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas
预防医学生物科学研究方法、生物科学研究技术生物工程学
Mercado Noe B.,Dalvie Neil C.,Kaur Kawaljit,McMahan Katherine,Yu Jingyou,Nampanya Felix,Brown Renita,Teow Elyse,Kleanthous Harry,Biswas Sumi,Martinot Amanda J.,Giffin Victoria M.,Yun Dongsoo,Chang Aiquan,Chandrashekar Abishek,Naranjo Christopher A.,Camp Danielle L.,Rodriguez-Aponte Sergio A,Love J. Christopher,Barouch Dan H.,Bajoria Sakshi,Pessaint Laurent,Velasco Jason,Patel Shivani,Bowman Lesley,Tostanoski Lisa H.,Silverman Judith Maxwell,Andersen Hanne,Volkin David B.,Cook Anthony,Joshi Sangeeta B.,Flinchbaugh Zach,Lewis Mark G.,Kumru Ozan S..A modular protein subunit vaccine candidate produced in yeast confers protection against SARS-CoV-2 in non-human primates[EB/OL].(2025-03-28)[2025-04-26].https://www.biorxiv.org/content/10.1101/2021.07.13.452251.点此复制
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