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

doi:10.1016/j.jacig.2023.100129

. 2023 Jun 25;2(4):100129.

doi: 10.1016/j.jacig.2023.100129. eCollection 2023 Nov.

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

Kevin T Cao¹, Catalina Cobos-Uribe¹, Noelle Knight², Rithika Jonnalagadda³, Carole Robinette², Ilona Jaspers^{1

2

4}, Meghan E Rebuli^{1

2

4}

Affiliations

¹ Curriculum in Toxicology and Environmental Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
² Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
³ UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC.
⁴ Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC.

PMID: 37781659
PMCID: PMC10290737
DOI: 10.1016/j.jacig.2023.100129

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

Kevin T Cao et al. J Allergy Clin Immunol Glob. 2023.

. 2023 Jun 25;2(4):100129.

doi: 10.1016/j.jacig.2023.100129. eCollection 2023 Nov.

Authors

Kevin T Cao¹, Catalina Cobos-Uribe¹, Noelle Knight², Rithika Jonnalagadda³, Carole Robinette², Ilona Jaspers^{1

2

4}, Meghan E Rebuli^{1

2

4}

Affiliations

¹ Curriculum in Toxicology and Environmental Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
² Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
³ UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC.
⁴ Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC.

PMID: 37781659
PMCID: PMC10290737
DOI: 10.1016/j.jacig.2023.100129

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.

Keywords: NELF; SARS-CoV-2; antibodies; antigens; epitope; mRNA vaccine; mucosal immune response; neutralization; serum; systemic immune response.

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Figures

**Fig 1**
Preimmunity and postimmunity SARS-CoV-2 virus–specific IgG and IgA antibody concentrations in NELF and serum. Antibody concentrations were reported as log₁₀ values. A, NELF IgA. B, NELF IgG. C, Serum IgA. D, Serum IgG. Unpaired t test and Mann-Whitney test with Shapiro Wilk normality testing. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001. Figures generated in GraphPad Prism 9.2.0.

**Fig 2**
Ratio of postimmunity SARS-CoV-2 S1 RBD and NTD to Spike-specific antibody concentrations in NELF and serum. A, NELF IgA. B, NELF IgG. C, Serum IgA. D, Serum IgG. Figures generated in GraphPad Prism 9.2.0.

**Fig 3**
Comirnaty and Spikevax postimmunity SARS-CoV-2 virus–specific IgG and IgA antibody concentrations in NELF and serum. Antibody concentrations were reported as log₁₀ values. A, NELF IgA. B, NELF IgG. C, Serum IgA. D, Serum IgG. Unpaired t test and Mann-Whitney test with Shapiro Wilk normality testing. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001. Figures generated in GraphPad Prism 9.2.0.

**Fig 4**
Postimmunity SARS-CoV-2 S1 RBD–specific neutralization activity in NELF and serum. A, Percent inhibition in NELF and serum. B, Percent inhibition (reported as AU/mL) in NELF and serum. C, Percent inhibition comparing Comirnaty and Spikevax in NELF and serum. D, Percent inhibition (reported as AU/mL) comparing the Comirnaty and Spikevax vaccines in NELF and serum. Unpaired t test and Mann-Whitney test with Shapiro-Wilk normality testing. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001. Figures generated in GraphPad Prism 9.2.0.

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References

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[1] Gallo O., Locatello L.G., Mazzoni A., Novelli L., Annunziato F. The central role of the nasal microenvironment in the transmission, modulation, and clinical progression of SARS-CoV-2 infection. Mucosal Immunol. 2021;14:305–316. - PMC - PubMed

[2] Gallo O., Locatello L.G., Mazzoni A., Novelli L., Annunziato F. The central role of the nasal microenvironment in the transmission, modulation, and clinical progression of SARS-CoV-2 infection. Mucosal Immunol. 2021;14:305–316. - PMC - PubMed

[3] Gianchecchi E., Manenti A., Kistner O., Trombetta C., Manini I., Montomoli E. How to assess the effectiveness of nasal influenza vaccines? Role and measurement of sIgA in mucosal secretions. Influenza Other Respir Viruses. 2019;13:429–437. - PMC - PubMed

[4] Gianchecchi E., Manenti A., Kistner O., Trombetta C., Manini I., Montomoli E. How to assess the effectiveness of nasal influenza vaccines? Role and measurement of sIgA in mucosal secretions. Influenza Other Respir Viruses. 2019;13:429–437. - PMC - PubMed

[5] Janeway C., editor. Immunobiology: the immune system in health and disease [animated CD-ROM inside] 5th ed. Garland Publishing; New York, NY: 2001. p. 732.

[6] Janeway C., editor. Immunobiology: the immune system in health and disease [animated CD-ROM inside] 5th ed. Garland Publishing; New York, NY: 2001. p. 732.

[7] Ainai A., Suzuki T., Tamura S.I., Hasegawa H. intranasal administration of whole inactivated influenza virus vaccine as a promising influenza vaccine candidate. Viral Immunol. 2017;30:451–462. - PubMed

[8] Ainai A., Suzuki T., Tamura S.I., Hasegawa H. intranasal administration of whole inactivated influenza virus vaccine as a promising influenza vaccine candidate. Viral Immunol. 2017;30:451–462. - PubMed

[9] Steffen U., Koeleman C.A., Sokolova M.V., Bang H., Kleyer A., Rech J., et al. IgA subclasses have different effector functions associated with distinct glycosylation profiles. Nat Commun. 2020;11:120. - PMC - PubMed

[10] Steffen U., Koeleman C.A., Sokolova M.V., Bang H., Kleyer A., Rech J., et al. IgA subclasses have different effector functions associated with distinct glycosylation profiles. Nat Commun. 2020;11:120. - PMC - PubMed

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

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

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