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<p>Respiratory viral infections, such as influenza and coronavirus, are major threats to humankind. Injectable vaccines for SARS-CoV-2 protect against severe disease but fail to induce immunity in the upper airway mucosa, the virus entry site, thus not preventing infection and transmission. This highlights the urgent need for mucosal-targeted vaccination systems. While intranasal immunization holds promise, achieving local antigen delivery for mucosal immunity remains challenging. To address this, we designed an innovative nanoparticle system to deliver intranasal vaccines, using the receptor-binding domain (RBD) and multiple T-cell epitopes of SARS-CoV-2 antigens. Nonporous silica-based nanoparticles (SiNP) functionalized with a mucoadhesive cyclodextrin polymer (MaP) were selected as a delivery vehicle capable of adhering to and penetrating mucus. In a 3-dose regimen, the nanovaccine induced and sustained high systemic and neutralizing antibody levels for at least 1 year, with robust cellular responses, as well as IgA secretion in the oral and nasal cavities, providing strong protection against SARS-CoV-2 and substantially reducing viral loads in both upper and lower respiratory tracts. Our findings provide evidence that an intranasal vaccination platform combining two distinct nanoscale strategies might be crucial for inducing lasting and broad systemic and upper airway immunity, potentially controlling SARS-CoV-2 infection and transmission.</p>

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An innovative nasal nanovaccine against SARS-CoV-2 induces systemic and upper airway immunity controlling viral replication

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月4日

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  • Roberta L. Pagni,
  • Edecio Cunha-Neto,
  • Yasmin da Silva Santos,
  • Edilberto Postól,
  • Raquel Elaine de Alencar,
  • Ana Moretti,
  • Jonnatan J. Santos,
  • Tamires L. Silva,
  • Isabela P. Daher,
  • Marcos C. Knirsch,
  • João Paulo S. Nunes,
  • Sergio H. Toma,
  • Koiti Araki,
  • Cesar Remuzgo,
  • Lucas Cauê Jacintho,
  • Lea Maria Demarchi,
  • Vivian Leite de Oliveira,
  • Verônica Coelho,
  • Silvia Beatriz Boscardin,
  • Daniela S. Rosa,
  • João Victor Batalha-Carvalho,
  • Ana Maria Moro,
  • Keity S. Santos,
  • Marco Antonio Stephano,
  • Jorge Kalil,
  • Ana Carolina Ares,
  • Andreia Cristina Kazue Kuramoto Takara,
  • Jamille Ramos de Oliveira,
  • Marcio Massao Yamamoto,
  • Maria Lucia Carnevale Marin,
  • Philippe Rodrigues Benedetti,
  • Rafael Ribeiro Almeida,
  • Samar Freschi de Barros,
  • Sandra Maria Monteiro,
  • Selma Aliotti Palacios,
  • Simone Regina dos Santos,
  • Washington Robert da Silva

摘要

Respiratory viral infections, such as influenza and coronavirus, are major threats to humankind. Injectable vaccines for SARS-CoV-2 protect against severe disease but fail to induce immunity in the upper airway mucosa, the virus entry site, thus not preventing infection and transmission. This highlights the urgent need for mucosal-targeted vaccination systems. While intranasal immunization holds promise, achieving local antigen delivery for mucosal immunity remains challenging. To address this, we designed an innovative nanoparticle system to deliver intranasal vaccines, using the receptor-binding domain (RBD) and multiple T-cell epitopes of SARS-CoV-2 antigens. Nonporous silica-based nanoparticles (SiNP) functionalized with a mucoadhesive cyclodextrin polymer (MaP) were selected as a delivery vehicle capable of adhering to and penetrating mucus. In a 3-dose regimen, the nanovaccine induced and sustained high systemic and neutralizing antibody levels for at least 1 year, with robust cellular responses, as well as IgA secretion in the oral and nasal cavities, providing strong protection against SARS-CoV-2 and substantially reducing viral loads in both upper and lower respiratory tracts. Our findings provide evidence that an intranasal vaccination platform combining two distinct nanoscale strategies might be crucial for inducing lasting and broad systemic and upper airway immunity, potentially controlling SARS-CoV-2 infection and transmission.