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

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Citações na Scopus
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Tipo de produção
article
Data de publicação
2023
Título da Revista
ISSN da Revista
Título do Volume
Editora
MDPI
Autores
RUSSO, Momtchilo
LINS, Bruna B.
KERSTEN, Victor
PERNAMBUCO, Paulo C. A.
GOMES, Brisa Moreira
DATI, Livia Mendonca Munhoz
Citação
VACCINES, v.11, n.11, article ID 1732, 17p, 2023
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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.
Palavras-chave
SARS-CoV-2, vaccine, hACE2 transgenic mice, intranasal route, spike protein, cationic liposome, CpG-ODNs, heterologous immunity
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