An innovative nasal nanovaccine against SARS-CoV-2 induces systemic and upper airway immunity controlling viral replication
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.
Authors
- João Victor Batalha-Carvalho (ORCID: https://orcid.org/0000-0002-1526-6915)
- Edilberto Postól
- Ana Iochabel Soares Moretti (ORCID: https://orcid.org/0000-0003-3402-5778)
- Márcio Yamamoto (ORCID: https://orcid.org/0000-0003-1993-8608)
- Marco Antônio Stephano (ORCID: https://orcid.org/0000-0003-2927-0584)
- Sérgio H. Toma (ORCID: https://orcid.org/0000-0002-3003-7889)
- Vivian L. de Oliveira (ORCID: https://orcid.org/0000-0003-2523-0374)
- Ana Maria Moro (ORCID: https://orcid.org/0000-0002-0650-7764)
- Verônica Coelho (ORCID: https://orcid.org/0000-0002-0989-2581)
- T. C. Silva
- Samar Freschi Barros
- Maria Lúcia Carnevale Marin (ORCID: https://orcid.org/0000-0002-5278-675X)
- Silvia Beatriz Boscardin (ORCID: https://orcid.org/0000-0002-7845-7110)
- Roberta Liberato Pagni (ORCID: https://orcid.org/0000-0002-5516-7743)
- J. Kalil
- Lucas Cauê Jacintho (ORCID: https://orcid.org/0000-0003-1510-0218)
- Andréia Cristina Kazue Kuramoto Takara
- Washington Robert da Silva
- Simone Regina dos SANTOS
- Marcos Camargo Knirsch (ORCID: https://orcid.org/0000-0002-5311-1236)
- Daniela Santoro Rosa (ORCID: https://orcid.org/0000-0003-4536-891X)
- Isabela Pazotti Daher (ORCID: https://orcid.org/0000-0002-5699-0619)
- Sandra Maria Monteiro (ORCID: https://orcid.org/0000-0003-0481-6245)
- Selma A. Palácios
- Philippe Rodrigues Benedetti
- Jamille Ramos de Oliveira
- Raquel Alencar
- Rafael Ribeiro Almeida
- Jonnatan J. Santos
- Koiti Araki
- Edecio Cunha-Neto
- Keity S. Santos
- Ana Carolina Ares
- Cesar Remuzgo
- Yasmin da Silva Santos
- Lea Maria Demarchi
- On behalf of COVID-19 Brazil Team
- João Paulo S. Nunes
Institutions
- Universidade de São Paulo (BR)
- Instituto Butantan (BR)
- Instituto Nacional de Tecnologia (BR)
- Instituto de Ciências Farmacêuticas (BR)
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR)
- Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (BR)
- Associação Brasileira de Alergia e Imunologia (BR)
- Universidade Federal de São Paulo (BR)
Publication Details
- Journal
- npj Vaccines
- Published
- 2026-03-04
- DOI
- https://doi.org/10.1038/s41541-026-01407-x
- Primary Topic
- Advanced Drug Delivery Systems
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Financiadora de Estudos e Projetos
- Universidade de São Paulo