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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月18日

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

摘要

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.