94% of researchers rate our articles as excellent or good
Learn more about the work of our research integrity team to safeguard the quality of each article we publish.
Find out more
ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1524477
This article is part of the Research Topic Broad Spectrum Viral Vaccines View all 5 articles
Mucosal multivalent NDV-based vaccine provides cross-reactive immune responses against SARS-CoV-2 variants in animal models
Provisionally accepted
Irene González-Domínguez 
Adam Abdeljawad 
Tsoi-Ying Lai 
Marta Boza Stephen Mccroskery Nicholas Lemus Stefan Slamanig Gagandeep Singh 
Prajakta Warang 
Temima Yellin 
Anass Abad 
Juan Manuel Carreño Victoria Dolange Jose Luis Martínez-Guevara 
Gagandeep Singh Marina Barcena-Varela 
Lauren Chang 
Michael Schotsaert 
Florian Krammer 
Peter Palese *
Weina Sun *- Icahn School of Medicine at Mount Sinai, New York, United States
A new generation of mucosal vaccine against the ever-evolving SARS-CoV-2 is of great value to fight COVID-19. In previous studies, our groups developed a viral vector vaccine based on an avirulent Newcastle disease virus (NDV) expressing the prefusion-stabilized spike protein of SARS-CoV-2 (NDV-HXP-S). Here we characterized the in vivo biodistribution and immunogenicity of a live mucosal NDV-HXP-S vaccine in animal models. NDV showed restricted replication in mice and hamsters. Despite limited replication, intranasal live NDV-HXP-S provided protection against SARS-CoV-2 challenge and direct-contact transmission in hamsters. Importantly, a trivalent live NDV-HXP-S vaccine (Wuhan, Beta, Delta) induced more cross-reactive antibody responses against the phylogenetically distant Omicron variant than the ancestral vaccine. Furthermore, intranasal trivalent live NDV-HXP-S boosted systemic and mucosal immunity in mice pre-immunized with mRNA vaccine. Overall, a mucosal multivalent live NDV-HXP-S vaccine shows great promise as a safe, next-generation vaccine conferring broad mucosal and systemic immunity against future SARS-CoV-2 variants.
Keywords: Transmission-proof, sterilizing immunity, viral shedding, COVID-19, Coronavirus, Vector vaccine
Received: 07 Nov 2024; Accepted: 26 Feb 2025.
Copyright: © 2025 González-Domínguez, Abdeljawad, Lai, Boza, Mccroskery, Lemus, Slamanig, Singh, Warang, Yellin, Abad, Carreño, Dolange, Martínez-Guevara, Singh, Barcena-Varela, Chang, Schotsaert, Krammer, Palese and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Peter Palese, Icahn School of Medicine at Mount Sinai, New York, United States
Weina Sun, Icahn School of Medicine at Mount Sinai, New York, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.