Modular protein subunit vaccine candidate produced in yeast protects against SARS-CoV-2 in non-human primates

  

View ORCID ProfileNeil C. Dalvie, Lisa H. Tostanoski, Sergio A Rodriguez-Aponte, Kawaljit Kaur, Sakshi Bajoria, Ozan S. Kumru, Amanda J. Martinot, Abishek Chandrashekar, Katherine McMahan, Noe B. Mercado, Jingyou Yu, Aiquan Chang, Victoria M. Giffin, Felix Nampanya, Shivani Patel, Lesley Bowman, Christopher A. Naranjo, Dongsoo Yun, Zach Flinchbaugh, Laurent Pessaint, Renita Brown, Jason Velasco, Elyse Teow, Anthony Cook, Hanne Andersen, Mark G. Lewis, Danielle L. Camp, Judith Maxwell Silverman, Harry Kleanthous, Sangeeta B. Joshi, David B. Volkin, Sumi Biswas,  View ORCID ProfileJ. Christopher Love, Dan H. Barouch

doi: https://doi.org/10.1101/2021.07.13.452251

This article is a preprint and has not been certified by peer review [what does this mean?].

PDF: https://www.biorxiv.org/content/10.1101/2021.07.13.452251v1.full.pdf

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.

Competing Interest Statement

J.C.L. has interests in Sunflower Therapeutics PBC, Pfizer, Honeycomb Biotechnologies, OneCyte Biotechnologies, QuantumCyte, Amgen, and Repligen. J.C.L's interests are reviewed and managed under MIT's policies for potential conflicts of interest. J.M.S. is an employee of the Bill & Melinda Gates Medical Research Institute. H.K. is an employee of the Bill & Melinda Gates Foundation. Sumi Biswas is the CEO and co-founder of SpyBiotech Ltd. which holds the exclusive rights for the use of Spytag/Spyctacher in the field of vaccines. Lesley Bowman is an employee of SpyBiotech Ltd.

https://www.biorxiv.org/content/10.1101/2021.07.13.452251v1