Trivalent NDV-HXP-S Vaccine Protects against Phylogenetically Distant SARS-CoV-2 Variants of Concern in Mice

Irene González-Domínguez, Jose Luis Martínez, Stefan Slamanig, Nicholas Lemus, Yonghong Liu, Tsoi Ying Lai, Juan Manuel Carreño, Gagandeep Singh, Gagandeep Singh, Michael Schotsaert, Ignacio Mena, Stephen McCroskery, Lynda Coughlan, Florian Krammer, Adolfo García-Sastre, Peter Palese, Weina Sun

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Equitable access to vaccines is necessary to limit the global impact of the coronavirus disease 2019 (COVID-19) pandemic and the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. In previous studies, we described the development of a low-cost vaccine based on a Newcastle Disease virus (NDV) expressing the prefusion-stabilized spike protein from SARS-CoV-2, named NDV-HXP-S. Here, we present the development of next-generation NDV-HXP-S variant vaccines, which express the stabilized spike protein of the Beta, Gamma, and Delta variants of concerns (VOC). Combinations of variant vaccines in bivalent, trivalent, and tetravalent formulations were tested for immunogenicity and protection in mice. We show that the trivalent preparation, composed of the ancestral Wuhan, Beta, and Delta vaccines, substantially increases the levels of protection and of cross-neutralizing antibodies against mismatched, phylogenetically distant variants, including the currently circulating Omicron variant. IMPORTANCE This manuscript describes an extended work on the Newcastle disease virus (NDV)-based vaccine focusing on multivalent formulations of NDV vectors expressing different prefusion-stabilized versions of the spike proteins of different SARS-CoV-2 variants of concern (VOC). We demonstrate here that this low-cost NDV platform can be easily adapted to construct vaccines against SARS-CoV-2 variants. Importantly, we show that the trivalent preparation, composed of the ancestral Wuhan, Beta, and Delta vaccines, substantially increases the levels of protection and of cross-neutralizing antibodies against mismatched, phylogenetically distant variants, including the currently circulating Omicron variant. We believe that these findings will help to guide efforts for pandemic preparedness against new variants in the future.

Original languageEnglish
JournalMicrobiology spectrum
Volume10
Issue number3
DOIs
StatePublished - Jun 2022

Keywords

  • cross-protection
  • low-cost vaccine platform
  • multivalent vaccine
  • neutralizing antibodies
  • pandemic preparedness

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