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Front Immunol . Mucosal multivalent NDV-based vaccine provides cross-reactive immune responses against SARS-CoV-2 variants in animal models

tetano

Editor, Senior Moderator
Front Immunol


. 2025 Mar 17:16:1524477.
doi: 10.3389/fimmu.2025.1524477. eCollection 2025. Mucosal multivalent NDV-based vaccine provides cross-reactive immune responses against SARS-CoV-2 variants in animal models

Irene González-Domínguez[SUP] 1 [/SUP], Adam Abdeljawad[SUP] 1 [/SUP], Tsoi Ying Lai[SUP] 1 [/SUP], Marta Boza[SUP] 1 [/SUP], Stephen McCroskery[SUP] 1 [/SUP], Nicholas Lemus[SUP] 1 [/SUP], Stefan Slamanig[SUP] 1 2 [/SUP], Gagandeep Singh[SUP] 1 3 [/SUP], Prajakta Warang[SUP] 1 3 [/SUP], Temima Yellin[SUP] 1 [/SUP], Anass Abbad[SUP] 1 [/SUP], Juan Manuel Carreño[SUP] 1 [/SUP], Victoria Dolange[SUP] 1 [/SUP], Jose Luis Martínez-Guevara[SUP] 1 [/SUP], Gagandeep Singh[SUP] 1 [/SUP], Marina Barcena-Varela[SUP] 4 [/SUP], Lauren A Chang[SUP] 1 3 [/SUP], Michael Schotsaert[SUP] 1 3 5 6 [/SUP], Florian Krammer[SUP] 1 7 8 9 [/SUP], Peter Palese[SUP] 1 10 [/SUP], Weina Sun[SUP] 1 [/SUP]



Affiliations
Abstract

Introduction: 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).
Methods: Here we characterized the in vivo biodistribution and immunogenicity of a live mucosal NDV-HXP-S vaccine in animal models.
Results: 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.
Discussion: 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: COVID-19; Coronavirus; sterilizing immunity; transmission-proof; vector vaccine; viral shedding.

 
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