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

Publication date: Nov 20, 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.

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Concepts Keywords
Agonist cationic liposome
Astrazeneca CpG-ODNs
Chimpanzee hACE2 transgenic mice
Vaccine heterologous immunity
Wild intranasal route
SARS-CoV-2
spike protein
vaccine

Semantics

Type Source Name
disease MESH SARS-CoV-2 Infection
pathway REACTOME SARS-CoV-2 Infection
disease VO vaccination
disease VO vaccine candidate
disease VO Toll-like receptor
disease VO vaccine
disease VO intranasal vaccination
disease MESH infection
disease MESH weight loss
disease VO intranasal route
disease VO effective
disease VO intramuscular vaccination
disease IDO replication
disease VO Glycoprotein
disease IDO production
drug DRUGBANK Dimercaprol
drug DRUGBANK Ribostamycin
drug DRUGBANK Coenzyme M
disease VO CoronaVac
disease VO efficient
disease VO immunization
disease MESH death
disease MESH morbidity
disease VO time
disease VO organization
disease VO USA
disease VO vaccine dose
disease VO volume
disease VO vaccination protocol
disease IDO blood
drug DRUGBANK Alpha-Linolenic Acid
drug DRUGBANK Alkaline Phosphatase
drug DRUGBANK Urea
drug DRUGBANK Creatinine
drug DRUGBANK Calcium
drug DRUGBANK Phosphorus
drug DRUGBANK Dextrose unspecified form
drug DRUGBANK Cholesterol
disease VO urinary bladder
disease VO stomach
disease VO protocol
disease VO viability
disease VO viable
drug DRUGBANK L-Phenylalanine
drug DRUGBANK Dimethyl sulfoxide
disease IDO pathogen
disease MESH virus infection
drug DRUGBANK Water
disease VO vaccinated
drug DRUGBANK Phosphate ion
drug DRUGBANK Ketamine
drug DRUGBANK Xylazine
disease VO injection
disease MESH ataxia
drug DRUGBANK Isoflurane
disease IDO assay
disease VO inactivation
disease VO gene
drug DRUGBANK Thiocolchicoside
drug DRUGBANK Trihexyphenidyl
drug DRUGBANK Timonacic
disease VO Tat
disease VO TTC
drug DRUGBANK Sodium acetate
drug DRUGBANK Acetic acid
disease VO antibody titer
disease VO ANOVA
disease VO regulatory agency
disease VO dose
disease MESH lung adenocarcinoma
disease MESH noma
disease IDO site
disease MESH brain inflammation
disease MESH neuroinflammation
disease VO effectiveness
disease VO population
disease VO efficiency
disease VO vein
disease VO URE
drug DRUGBANK Diphenylpyraline
disease MESH asthma
pathway KEGG Asthma
disease VO immunized
disease IDO cell
disease IDO facility
disease MESH Severe Acute Respiratory Syndrome
disease VO SARS vaccine
drug DRUGBANK Sulfasalazine
disease MESH Oxidative Stress
drug DRUGBANK (S)-Des-Me-Ampa
disease MESH Pneumonia
drug DRUGBANK Efavirenz
disease VO Ad26.COV2.S

Original Article

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