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, Adolfo García-Sastre, Florian Krammer, Ralph S. Baric, Peter Palese

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

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.

Original languageEnglish
Article number103132
JournaleBioMedicine
Volume62
DOIs
StatePublished - Dec 2020

Keywords

  • Coronavirus vaccine
  • Intramuscular administration
  • Live COVID-19 vaccine
  • Mouse-adapted SARS-CoV-2
  • Neutralizing antibodies
  • Viral vector vaccine

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