Intranasal spike and nucleoprotein fusion protein-based vaccine provides cross-protection and reduced transmission against SARS-CoV-2 variants

The effectiveness of intramuscular vaccines aimed at preventing severe COVID-19 remains limited due to waning immunity and the emergence of novel variants. Next-generation vaccines are needed for broader protection and blocking virus transmission. Here, we rationally designed an original nasal subunit vaccine composed of a fusion protein (SwFN) made of Wuhan spike and nucleoprotein combined with biocompatible mucosal nanocarriers (Nc). In mouse model, the nasal Nc-SwFN vaccine elicited multivalent serum and mucosal neutralizing antibodies. Robust spike and nucleoprotein cross-reactive immunity against variants was induced with a predominant phenotype of resident memory T cells in the lungs. Moreover, Nc-SwFN led to protective responses against Wuhan and Delta infection in relevant models with an absence of morbidity, mortality, and virus dissemination in the lungs and brain. Finally, Nc-SwFN drastically reduced host-to-host transmission. These promising results underscore the advantages of the nasal Nc-SwFN approach as a broad-spectrum vaccine candidate against current and emerging SARS-CoV-2 variants.

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Publication Details

Journal
npj Vaccines
Published
2025-04-18
DOI
https://doi.org/10.1038/s41541-025-01123-y
Citations
1
Primary Topic
SARS-CoV-2 and COVID-19 Research
Type
article
Field-Weighted Citation Impact
1.40

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article

Intranasal spike and nucleoprotein fusion protein-based vaccine provides cross-protection and reduced transmission against SARS-CoV-2 variants

Nathalie Moiré, Amel Bouakane, Charles-Adrien Richard, Nicolas Aubrey et al.
1 citations
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SARS-CoV-2 and COVID-19 Research
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article

Intranasal spike and nucleoprotein fusion protein-based vaccine provides cross-protection and reduced transmission against SARS-CoV-2 variants

Nathalie Moiré, Amel Bouakane, Charles-Adrien Richard, Nicolas Aubrey, Jean‐François Eléouët, François Helle, Antoine Touzé, Mireille Caul-Futy, Zineb Lakhrif, Mickaël Riou, Laetitia Mérat, Stéphane Paul, Christelle Rossignol, Mathieu Epardaud, Céline Ducournau, Isabelle Dimier‐Poisson, Fanny Boursin, Rodolphe Carpentier, Yazdan Yazdanpanah, Stéphan Zientara, Fabienne Jospin, Marianne Maquart, Bernard Klonjkowski, Louis Lantier, Agathe Poupée-Beaugé, Nicolas Meunier, Sophie Le Poder, Marie-Noëlle Mévélec
article en
1 citations

Abstract

The effectiveness of intramuscular vaccines aimed at preventing severe COVID-19 remains limited due to waning immunity and the emergence of novel variants. Next-generation vaccines are needed for broader protection and blocking virus transmission. Here, we rationally designed an original nasal subunit vaccine composed of a fusion protein (SwFN) made of Wuhan spike and nucleoprotein combined with biocompatible mucosal nanocarriers (Nc). In mouse model, the nasal Nc-SwFN vaccine elicited multivalent serum and mucosal neutralizing antibodies. Robust spike and nucleoprotein cross-reactive immunity against variants was induced with a predominant phenotype of resident memory T cells in the lungs. Moreover, Nc-SwFN led to protective responses against Wuhan and Delta infection in relevant models with an absence of morbidity, mortality, and virus dissemination in the lungs and brain. Finally, Nc-SwFN drastically reduced host-to-host transmission. These promising results underscore the advantages of the nasal Nc-SwFN approach as a broad-spectrum vaccine candidate against current and emerging SARS-CoV-2 variants.

npj VaccinesVol. 10(1)
Université Claude Bernard Lyon 1 (FR), Université de Tours (FR), Institut National de la Recherche Agronomique (MA), Inserm (FR), École Nationale Vétérinaire d'Alfort (FR), Université de Lille (FR), Université Paris-Saclay (FR), Centre Hospitalier Universitaire de Lille (FR), Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR), Assistance Publique – Hôpitaux de Paris (FR), Virologie et Immunologie Moléculaires (FR), Physiologie de la Reproduction et des Comportements (FR), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (FR), Biologie des oiseaux et aviculture (FR), Lille Inflammation Research International Center (FR), Services déconcentrés d'appui à la recherche Val de Loire (FR), Hôpital Bichat-Claude-Bernard (FR), Genkyotex (Switzerland) (CH), Centre Hospitalier Universitaire de Saint-Étienne (FR), Centre International de Recherche en Infectiologie (FR), Institute for Translational Research in Inflammation (FR), Agents infectieux, résistance et chimiothérapie (FR)
Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation, Infrastructures en Biologie Santé et Agronomie, Université François-Rabelais, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
Zero hunger
Openalex Percentile: Top 22%
SARS-CoV-2 and COVID-19 Research
1.40
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