SARS-CoV-2 mRNA vaccination induces an intranasal mucosal response characterized by neutralizing antibodies

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine-induced systemic antibody profiles are well characterized; however, little is known about whether intranasal mucosal antibodies are induced or can neutralize virus in response to mRNA vaccination. OBJECTIVE: We sought to evaluate intranasal mucosal antibody production with SARS-CoV-2 mRNA vaccination. METHODS: SARS-CoV-2–specific IgG and IgA concentrations and neutralization activity from sera and nasal mucosa via nasal epithelial lining fluid (NELF) collection were measured in SARS-CoV-2 mRNA–vaccinated healthy volunteers (N = 29) by using multiplex immunoassays. Data were compared before and after vaccination, between mRNA vaccine brands, and by sex. RESULTS: SARS-CoV-2 mRNA vaccination induced an intranasal immune response characterized by neutralizing mucosal antibodies. IgG antibodies displayed greater Spike 1 (S1) binding specificity than did IgA in serum and nasal mucosa. Nasal antibodies displayed greater neutralization activity against the receptor-binding domain than serum. Spikevax (Moderna)-vaccinated individuals displayed greater SARS-CoV-2–specific IgG and IgA antibody concentrations than did Comirnaty (BioNTech/Pfizer)-vaccinated individuals in their serum and nasal epithelial lining fluid. Sex-dependent differences in antibody response were not observed. CONCLUSION: SARS-CoV-2 mRNA vaccination induces a robust systemic and intranasal antibody production with neutralizing capacity. Spikevax vaccinations elicit a greater antibody response than does Comirnaty vaccination systemically and intranasally.