Induction of mucosal immune responses against SARS-CoV-2: a heterologous intramuscular mRNA-LNP prime/pulmonary recombinant subunit pull vaccination strategy.

ingentiumby ingentium

In Vaccines Literature.

Publication date: Jul 03, 2026

Approved mRNA vaccines administered intramuscularly (i. m.) induce strong systemic immune responses, but provide limited protection at the respiratory mucosa, where many infections are initiated. Designing safe and efficacious mucosal vaccines is challenging because it requires vaccine administration at the mucosa that is equipped with protective barriers and characterized by tolerogenic predominance. Here we show that i. m. prime immunization of mice with lipid nanoparticles (LNPs) loaded with mRNA encoding the SARS-CoV-2 spike protein, followed by pulmonary pull immunization with either mRNA-LNPs or spike protein adjuvanted with cationic adjuvant formulation (CAF)01 induce high systemic immune responses and virus-neutralizing spike-specific antibody responses in the lungs. However, only pulmonary pull immunization with CAF01-adjuvanted spike protein induces spike-specific mucosal antibody and lung-resident T-cell responses in the respiratory tract. This suggests that i. m. priming of strong immune responses with mRNA-LNPs combined with mucosal pull immunization with a subunit vaccine can re-direct the immune response to the respiratory mucosa.

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Concepts Keywords
Lipid nanoparticles
mRNA
Mucosal
SARS-CoV-2
Vaccine

Semantics

Type Source Name
disease MESH infections
pathway REACTOME Reproduction
disease MESH included
disease MESH severe acute respiratory syndrome
disease MESH breakthrough infections
disease MESH reinfection
disease MESH COVID 19
drug DRUGBANK Cholesterol
drug DRUGBANK Polyethylene glycol
drug DRUGBANK Phosphate ion
drug DRUGBANK Distearyldimonium
drug DRUGBANK Trehalose
drug DRUGBANK Sodium Citrate
drug DRUGBANK Sodium lauryl sulfate
disease MESH SDS
drug DRUGBANK Water
drug DRUGBANK Ethanol
disease MESH PBS
drug DRUGBANK Tromethamine
drug DRUGBANK Sucrose
drug DRUGBANK Nitrogen
drug DRUGBANK Glycerin
drug DRUGBANK Isoflurane
drug DRUGBANK Xylazine
drug DRUGBANK Ketamine
disease MESH flushing
drug DRUGBANK Human Serum Albumin
drug DRUGBANK Collagenase clostridium histolyticum
drug DRUGBANK Streptomycin
disease MESH APC
disease MESH FBS
drug DRUGBANK Carbonate ion
disease MESH Tec
drug DRUGBANK Methionine
disease MESH weight loss
disease MESH body weight
disease MESH sneezing
drug DRUGBANK Medical air
disease MESH LNs
disease MESH strain
pathway KEGG Viral replication
drug DRUGBANK Uridine
drug DRUGBANK Cytidine
disease MESH infectious diseases
disease MESH fibrosis
pathway REACTOME Translation
drug DRUGBANK Sodium Tetradecyl Sulfate
disease MESH Sid
drug DRUGBANK Etoperidone
disease MESH Emergencies
disease MESH Dis
disease MESH Lam
pathway REACTOME Release
disease MESH lung disease
disease MESH tuberculosis
pathway KEGG Tuberculosis
disease MESH Ad5
disease MESH acute respiratory distress syndrome
disease MESH Coronavirus Infection
disease MESH Virus Infections
disease MESH influenza

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