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Updated: Sep 28, 2025
Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
Trivalent NDV-HXP-S vaccine protects against phylogenetically distant SARS-CoV-2 variants of concern in mice
Irene González-Domínguez1, Jose Luis Martínez1, Stefan Slamanig1
1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
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.
Insights
Next-generation vaccines targeting COVID-19 variants were developed using Newcastle Disease virus. A trivalent vaccine combining ancestral, Beta, and Delta strains significantly boosted protection and cross-neutralizing antibodies against diverse SARS-CoV-2 variants.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Equitable access to COVID-19 vaccines is crucial for global pandemic control and preventing the emergence of new SARS-CoV-2 variants.
- Previous research established NDV-HXP-S, a low-cost vaccine expressing the prefusion stabilized spike protein of SARS-CoV-2.
- The emergence of SARS-CoV-2 variants of concern (VOCs) necessitates updated vaccine strategies.
Approach:
- Developed next-generation NDV-HXP-S vaccines expressing stabilized spike proteins from Beta, Gamma, and Delta SARS-CoV-2 variants.
- Created bivalent, trivalent, and tetravalent formulations combining these variant vaccines.
- Assessed immunogenicity and protective efficacy of these formulations in mouse models.
Key Points:
- A trivalent vaccine formulation (ancestral Wuhan, Beta, Delta) demonstrated enhanced immunogenicity.
- This trivalent vaccine significantly increased protection against homologous and heterologous SARS-CoV-2 variants.
- Elevated levels of cross-neutralizing antibodies were observed against phylogenetically distant variants, including Omicron.
Conclusions:
- Next-generation NDV-HXP-S variant vaccines offer a promising strategy for broader COVID-19 protection.
- Trivalent formulations show potential for improved efficacy against current and emerging SARS-CoV-2 variants.
- This approach supports the development of accessible and effective vaccines to combat the ongoing pandemic.
