Intranasal Liposomal Formulation of Spike Protein Adjuvanted with CpG Protects and Boosts Heterologous Immunity of hACE2 Transgenic Mice to SARS-CoV-2 Infection.
Momtchilo RussoMaria Cássia Mendes-CorrêaBruna B LinsVictor KerstenPaulo C A Pernambuco FilhoToni Ricardo MartinsTânia Regina Tozetto-MendozaLucy Santos Vilas BoasBrisa Moreira GomesLivia Mendonça Munhoz DatiAmaro Nunes Duarte-NetoGustavo Roncoli ReigadoAna Beatriz Teixeira FredericoDanielle R de A de Brito E CunhaAnderson Vicente de PaulaJosé Igor G da SilvaCarlos Franciney Moreira VasconcelosFelipe S ChambergoViviane Abreu NunesAna Paula Dinis Ano BomLeda R CastilhoRodrigo A P MartinsMario Hiroyuki HirataLuciana MirottiPublished in: Vaccines (2023)
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.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- toll like receptor
- drug delivery
- coronavirus disease
- weight loss
- dna methylation
- wild type
- bariatric surgery
- early stage
- inflammatory response
- risk factors
- nuclear factor
- pulmonary hypertension
- type diabetes
- oxidative stress
- gene expression
- dna damage
- zika virus
- high glucose
- coronary artery disease
- dengue virus
- body mass index
- amino acid
- copy number
- insulin resistance