Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPRUSSO, MomtchiloMENDES-CORREA, Maria CassiaLINS, Bruna B.KERSTEN, VictorPERNAMBUCO, Paulo C. A.MARTINS, Toni RicardoTOZETTO-MENDOZA, Tania ReginaBOAS, Lucy Santos VilasGOMES, Brisa MoreiraDATI, Livia Mendonca MunhozDUARTE-NETO, Amaro NunesREIGADO, Gustavo RoncoliFREDERICO, Ana Beatriz T.CUNHA, Danielle R. de A.PAULA, Anderson Vicente deSILVA, Jose Igor G. daVASCONCELOS, Carlos F. MoreiraCHAMBERGO, Felipe S.NUNES, Viviane AbreuBOM, Ana Paula Dinis AnoCASTILHO, Leda R.MARTINS, Rodrigo A. P.HIRATA, Mario HiroyukiMIROTTI, LucianaTRIPP, Ralph A.2024-02-152024-02-152023VACCINES, v.11, n.11, article ID 1732, 17p, 2023https://observatorio.fm.usp.br/handle/OPI/57956Mucosal 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.engopenAccessSARS-CoV-2vaccinehACE2 transgenic miceintranasal routespike proteincationic liposomeCpG-ODNsheterologous immunityarticleCopyright MDPI10.3390/vaccines11111732ImmunologyMedicine, Research & Experimental2076-393X