Replicating bacterium-vectored vaccine expressing SARS-CoV-2 Membrane and Nucleocapsid proteins protects against severe COVID-19-like disease in hamsters

Author:

Jia QingmeiORCID,Bielefeldt-Ohmann HelleORCID,Maison Rachel M.ORCID,Masleša-Galić SašaORCID,Cooper Sarah K.ORCID,Bowen Richard A.,Horwitz Marcus A.ORCID

Abstract

AbstractTo generate an inexpensive readily manufactured COVID-19 vaccine, we employed the LVS ΔcapB vector platform, previously used to generate potent candidate vaccines against Select Agent diseases tularemia, anthrax, plague, and melioidosis. Vaccines expressing SARS-CoV-2 structural proteins are constructed using the LVS ΔcapB vector, a highly attenuated replicating intracellular bacterium, and evaluated for efficacy in golden Syrian hamsters, which develop severe COVID-19-like disease. Hamsters immunized intradermally or intranasally with a vaccine co-expressing the Membrane and Nucleocapsid proteins and challenged 5 weeks later with a high dose of SARS-CoV-2 are protected against severe weight loss and lung pathology and show reduced viral loads in the oropharynx and lungs. Protection correlates with anti-Nucleocapsid antibody. This potent vaccine should be safe; inexpensive; easily manufactured, stored, and distributed; and given the high homology between Membrane and Nucleocapsid proteins of SARS-CoV and SARS-CoV-2, potentially serve as a universal vaccine against the SARS subset of pandemic causing β-coronaviruses.

Funder

U.S. Department of Health & Human Services | National Institutes of Health

UCLA AIDS Institute and Charity Treks

Publisher

Springer Science and Business Media LLC

Subject

Pharmacology (medical),Infectious Diseases,Pharmacology,Immunology

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