Article Dans Une Revue NPJ vaccines Année : 2025

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

Zineb Lakhrif
Fanny Boursin
Louis Lantier
Nathalie Moiré
Mireille Caul-Futy
Antoine Touzé
Sophie Le Poder
Bernard Klonjkowski
Nicolas Meunier
Stéphan Zientara
Nicolas Aubrey

Résumé

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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hal-05046705 , version 1 (05-05-2025)

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Zineb Lakhrif, Agathe Poupée-Beaugé, Fanny Boursin, Céline Ducournau, Louis Lantier, et al.. Intranasal spike and nucleoprotein fusion protein-based vaccine provides cross-protection and reduced transmission against SARS-CoV-2 variants. NPJ vaccines, 2025, 10 (1), pp.75. ⟨10.1038/s41541-025-01123-y⟩. ⟨hal-05046705⟩
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