Newcastle disease virus (NDV) expressing the spike protein of SARS-CoV-2 as a live virus vaccine candidate
Weina Sun,
Sarah R. Leist,
Stephen McCroskery,
Yonghong Liu,
Stefan Slamanig,
Justine Oliva,
Fatima Amanat,
Alexandra Schäfer,
Kenneth H. Dinnon, III,
Adolfo García-Sastre,
Florian Krammer,
Ralph S. Baric,
Peter Palese
Affiliations
Weina Sun
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Sarah R. Leist
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
Stephen McCroskery
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Yonghong Liu
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Stefan Slamanig
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Justine Oliva
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Fatima Amanat
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Alexandra Schäfer
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
Kenneth H. Dinnon, III
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
Adolfo García-Sastre
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Global Health Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Florian Krammer
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Ralph S. Baric
Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
Peter Palese
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Corresponding author.
Background: Due to the lack of protective immunity of humans towards the newly emerged SARS-CoV-2, this virus has caused a massive pandemic across the world resulting in hundreds of thousands of deaths. Thus, a vaccine is urgently needed to contain the spread of the virus. Methods: Here, we describe Newcastle disease virus (NDV) vector vaccines expressing the spike protein of SARS-CoV-2 in its wild type format or a membrane-anchored format lacking the polybasic cleavage site. All described NDV vector vaccines grow to high titers in embryonated chicken eggs. In a proof of principle mouse study, the immunogenicity and protective efficacy of these NDV-based vaccines were investigated. Findings: We report that the NDV vector vaccines elicit high levels of antibodies that are neutralizing when the vaccine is given intramuscularly in mice. Importantly, these COVID-19 vaccine candidates protect mice from a mouse-adapted SARS-CoV-2 challenge with no detectable viral titer and viral antigen in the lungs. Interpretation: The results suggested that the NDV vector expressing either the wild type S or membrane-anchored S without the polybasic cleavage site could be used as live vector vaccine against SARS-CoV-2. Funding: This work is supported by an NIAID funded Center of Excellence for Influenza Research and Surveillance (CEIRS) contract, the Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract, philanthropic donations and NIH grants.
