Intranasal vaccination with a Newcastle disease virus-vectored vaccine protects hamsters from SARS-CoV-2 infection and disease
Bryce M. Warner, Lisa A. Santry, Alexander Leacy, Mable Chan, Phuc H. Pham, Robert Vendramelli, Yanlong Pei, Nikesh Tailor, Emelissa J. Valcourt, Anders Leung, Shihua He, Bryan D. Griffin, Jonathan Audet, Marnie Willman, Kevin Tierney, Alixandra Albietz, Kathy L. Frost, Jacob G. E. Yates, Robert C. Mould, Lily Chan, Yeganeh Mehrani, Jason P. Knapp, Jessica A. Minott, Logan Banadyga, David Safronetz, Heidi Wood, Stephanie A. Booth, Pierre Major, Byram W. Bridle, Leonardo Susta, Darwyn Kobasa, Sarah K. Wootton
Abstract
The pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19). Worldwide efforts are being made to develop vaccines to mitigate this pandemic. We engineered two recombinant Newcastle disease virus (NDV) vectors expressing either the full-length SARS-CoV-2 spike protein (NDV-FLS) or a version with a 19 amino acid deletion at the carboxy terminus (NDV-Δ19S). Hamsters receiving two doses (prime-boost) of NDV-FLS developed a robust SARS-CoV-2-neutralizing antibody response, with elimination of infectious virus in the lungs and minimal lung pathology at five days post-challenge. Single-dose vaccination with NDV-FLS significantly reduced SARS-CoV-2 replication in the lungs but only mildly decreased lung inflammation. NDV-Δ19S-treated hamsters had a moderate decrease in SARS-CoV-2 titers in lungs and presented with severe microscopic lesions, suggesting that truncation of the spike protein was a less effective strategy. In summary, NDV-vectored vaccines represent a viable option for protection against COVID-19.