Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Cao KT

PROVIDER: S-EPMC10290737 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Cao Kevin T KT Cobos-Uribe Catalina C Knight Noelle N Jonnalagadda Rithika R Robinette Carole C Jaspers Ilona I Rebuli Meghan E ME

The journal of allergy and clinical immunology. Global 20230625 4

<h4>Background</h4>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.<h4>Objective</h4>We sought to evaluate intranasal mucosal antibody production with SARS-CoV-2 mRNA vaccination.<h4>Methods</h4>SARS-CoV-2-specific IgG and IgA concentrations and neutralization activity from ser ...[more]

PMID: 37781659

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Project description:Two doses of BNT162b2 mRNA vaccine induces a strong systemic SARS-CoV-2 specific humoral response. However, SARS-CoV-2 airborne transmission makes mucosal immune response a crucial first line of defense. Therefore, we characterized SARS-CoV-2-specific IgG responses induced by BNT162b2 vaccine, as well as IgG responses to other pathogenic and seasonal human coronaviruses in oral fluid and plasma from 200 UK healthcare workers who were naïve (N=62) or previously infected with SARS-CoV-2 (N=138) using a pan-coronavirus multiplex binding immunoassay (Meso Scale Discovery®). Additionally, we investigated the impact of historical SARS-CoV-2 infection on vaccine-induced IgG, IgA and neutralizing responses in selected oral fluid samples before vaccination, after a first and second dose of BNT162b2, as well as following a third dose of mRNA vaccine or breakthrough infections using the same immunoassay and an ACE2 inhibition assay. Prior to vaccination, we found that spike-specific IgG levels in oral fluid positively correlated with IgG levels in plasma from previously-infected individuals (Spearman r=0.6858, p<0.0001) demonstrating that oral fluid could be used as a proxy for the presence of plasma SARS-CoV-2 IgG. However, the sensitivity was lower in oral fluid (0.85, 95% CI 0.77-0.91) than in plasma (0.94, 95% CI 0.88-0.97). Similar kinetics of mucosal and systemic spike-specific IgG levels were observed following vaccination in naïve and previously-infected individuals, respectively. In addition, a significant enhancement of OC43 and HKU1 spike-specific IgG levels was observed in previously-infected individuals following one vaccine dose in oral fluid (OC43 S: p<0.0001; HKU1 S: p=0.0423) suggesting cross-reactive IgG responses to seasonal beta coronaviruses. Mucosal spike-specific IgA responses were induced by mRNA vaccination particularly in previously-infected individuals (71%) but less frequently in naïve participants (23%). Neutralizing responses to SARS-CoV-2 ancestral and variants of concerns were detected following vaccination in naïve and previously-infected participants, with likely contribution from both IgG and IgA in previously-infected individuals (correlations between neutralizing responses and IgG: Spearman r=0.5642, p<0.0001; IgA: Spearman r=0.4545, p=0.0001). We also observed that breakthrough infections or a third vaccine dose enhanced mucosal antibody levels and neutralizing responses. These data contribute to show that a previous SARS-CoV-2 infection tailors the mucosal antibody profile induced by vaccination.

Dataset Information

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

Background

Objective

Methods

Results

Conclusion

Publications

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

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