Replicating bacterium-vectored vaccine expressing SARS-CoV-2 Membrane and Nucleocapsid proteins protects against severe COVID-19-like disease in hamsters
Qingmei Jia,
Helle Bielefeldt-Ohmann,
Rachel M. Maison,
Saša Masleša-Galić,
Sarah K. Cooper,
Richard A. Bowen,
Marcus A. Horwitz
Affiliations
Qingmei Jia
Division of Infectious Diseases, Department of Medicine, 37-121 Center for Health Sciences, School of Medicine, University of California – Los Angeles
Helle Bielefeldt-Ohmann
School of Veterinary Science, University of Queensland
Rachel M. Maison
Department of Biomedical Sciences, Colorado State University
Saša Masleša-Galić
Division of Infectious Diseases, Department of Medicine, 37-121 Center for Health Sciences, School of Medicine, University of California – Los Angeles
Sarah K. Cooper
Department of Microbiology, Immunology, and Pathology, Colorado State University
Richard A. Bowen
Department of Biomedical Sciences, Colorado State University
Marcus A. Horwitz
Division of Infectious Diseases, Department of Medicine, 37-121 Center for Health Sciences, School of Medicine, University of California – Los Angeles
Abstract To 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.
