Portal de Periódicos da CAPES

Artigo Acesso aberto Produção Nacional Revisado por pares

BIBTEX RIS

Intranasal Liposomal Formulation of Spike Protein Adjuvanted with CpG Protects and Boosts Heterologous Immunity of hACE2 Transgenic Mice to SARS-CoV-2 Infection

2023; Multidisciplinary Digital Publishing Institute; Volume: 11; Issue: 11 Linguagem: Inglês

10.3390/vaccines11111732

2076-393X

Momtchilo Russo, Maria Cássia Mendes-Corrêa, Bruna Bezerra Lins, Victor Kersten, Paulo C. A. Pernambuco Filho, Toni Ricardo Martins, Tânia Regina Tozetto‐Mendoza, Lucy Santos Vilas Boas, Brisa Moreira Gomes, Lívia Mendonça Munhoz Dati, Amaro Nunes Duarte‐Neto, Gustavo Roncoli Reigado, Ana Frederico, Danielle Brito e Cunha, Anderson Vicente de Paula, Josiane Ramos da Silva, Carlos Franciney Moreira Vasconcelos, Felipe S. Chambergo, Viviane Abreu Nunes, Ana Paula Dinis Ano Bom, Leda R. Castilho, Rodrigo A. P. Martins, Mário Hiroyuki Hirata, Luciana Mirotti,

Bacterial Infections and Vaccines

Mucosal vaccination appears to be suitable to protect against SARS-CoV-2 infection. In this study, we tested an intranasal mucosal vaccine candidate for COVID-19 that consisted of a cationic liposome containing a trimeric SARS-CoV-2 spike protein and CpG-ODNs, a Toll-like receptor 9 agonist, as an adjuvant. In vitro and in vivo experiments indicated the absence of toxicity following the intranasal administration of this vaccine formulation. First, we found that subcutaneous or intranasal vaccination protected hACE-2 transgenic mice from infection with the wild-type (Wuhan) SARS-CoV-2 strain, as shown by weight loss and mortality indicators. However, when compared with subcutaneous administration, the intranasal route was more effective in the pulmonary clearance of the virus and induced higher neutralizing antibodies and anti-S IgA titers. In addition, the intranasal vaccination afforded protection against gamma, delta, and omicron virus variants of concern. Furthermore, the intranasal vaccine formulation was superior to intramuscular vaccination with a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 spike glycoprotein (Oxford/AstraZeneca) in terms of virus lung clearance and production of neutralizing antibodies in serum and bronchial alveolar lavage (BAL). Finally, the intranasal liposomal formulation boosted heterologous immunity induced by previous intramuscular vaccination with the Oxford/AstraZeneca vaccine, which was more robust than homologous immunity.