ArticleIranian journal of basic medical sciences2026
Intranasal administration of spike-specific mRNA-LNP confers more protection than the intramuscular route against SARS-CoV-2.
Article in Iranian journal of basic medical sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objectives: Intranasal vaccination mimics natural infection and induces mucosal immunity against respiratory viruses. This study compared the immunogenicity and protective efficacy of a nucleoside-modified messenger RNA (mRNA) encoding the SARS-CoV-2 spike protein, encapsulated in lipid nanoparticles (LNPs), administered via intranasal (I.N) versus intramuscular (I.M) routes. Materials and Methods: BALB/c mice received mRNA-LNP vaccines at 1, 5, or 10 µg doses intramuscularly. Antibody responses (Immunoglobulin G/IgA [IgG/IgA]), neutralization titers (conventional virus neutralization test [cVNT]), and interferon-gamma (IFN-γ) responses were assessed to select the optimal dose. The selected 5 µg dose was then administered to mice and Syrian hamsters via I.N or I.M routes. Post-challenge, lung viral loads (50% Tissue Culture Infectious Dose [TCID Results: The 5 µg dose induced robust humoral and cellular immunity (cVNT >5 log₂). Intranasal delivery elicited strong spike-specific IgA in nasal washes. Although I.M vaccination produced higher serum neutralizing titers (51.2 vs. 22.0), I.N vaccination conferred superior protection with a 4-log reduction in lung viral load (~10¹ TCID Conclusion: Intranasal mRNA-LNP administration elicits potent mucosal and systemic immunity and provides superior protection against SARS-CoV-2 challenge compared to I.M vaccination, underscoring its promise as a transformative strategy for respiratory virus vaccines.
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