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Repeated COVID-19 mRNA-based vaccination contributes to SARS-CoV-2 neutralizing antibody responses in the mucosa

Jozefien Declercq (UGent) , Sarah Gerlo (UGent) , Sharon Van Nevel (UGent) , Natalie De Ruyck (UGent) , Gabriële Holtappels (UGent) , Liesbeth Delesie (UGent) , Els Tobback (UGent) , Inés Lammens (UGent) , Nikita Gerebtsov (UGent) , Koen Sedeyn (UGent) , et al.
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Abstract
To prevent infection by respiratory viruses and consequently limit virus circulation, vaccines need to promote mucosal immunity. The extent to which the currently used messenger RNA (mRNA)-based COVID-19 vaccines induce mucosal immunity remains poorly characterized. We evaluated mucosal neutralizing antibody responses in a cohort of 183 individuals. Participants were sampled at several time points after primary adenovirus vector-based or mRNA-based COVID-19 vaccination and after mRNA-based booster vaccinations. Our findings revealed that repeated vaccination with mRNA boosters promoted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies in nasal secretions. Nasal and serum neutralizing antibody titers of both IgG and IgA isotypes correlated to one another. We investigated the source of these mucosal antibodies in a mouse model wherein mice received repeated mRNA vaccines for SARS-CoV-2. These experiments indicated that neutralizing antibody-producing cells reside in the spleen and bone marrow, whereas no proof of tissue homing to the respiratory mucosa was observed, despite the detection of mucosal antibodies. Serum transfer experiments confirmed that circulating antibodies were able to migrate to the respiratory mucosa. Collectively, these results demonstrate that, especially upon repeated vaccination, the currently used COVID-19 mRNA vaccines can elicit mucosal neutralizing antibodies and that vaccination might also stimulate mucosal immunity induced by previous SARS-CoV-2 infection. Moreover, migration of circulating antibodies to the respiratory mucosa might be a main mechanism. These findings advance our understanding of mRNA vaccine-induced immunity and have implications for the design of vaccine strategies to combat respiratory infections.
Keywords
J-CHAIN, INDUCTION, IMMUNITY, CELLS

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Citation

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MLA
Declercq, Jozefien, et al. “Repeated COVID-19 MRNA-Based Vaccination Contributes to SARS-CoV-2 Neutralizing Antibody Responses in the Mucosa.” SCIENCE TRANSLATIONAL MEDICINE, vol. 16, no. 770, 2024, doi:10.1126/scitranslmed.adn2364.
APA
Declercq, J., Gerlo, S., Van Nevel, S., De Ruyck, N., Holtappels, G., Delesie, L., … Vanhee, S. (2024). Repeated COVID-19 mRNA-based vaccination contributes to SARS-CoV-2 neutralizing antibody responses in the mucosa. SCIENCE TRANSLATIONAL MEDICINE, 16(770). https://doi.org/10.1126/scitranslmed.adn2364
Chicago author-date
Declercq, Jozefien, Sarah Gerlo, Sharon Van Nevel, Natalie De Ruyck, Gabriële Holtappels, Liesbeth Delesie, Els Tobback, et al. 2024. “Repeated COVID-19 MRNA-Based Vaccination Contributes to SARS-CoV-2 Neutralizing Antibody Responses in the Mucosa.” SCIENCE TRANSLATIONAL MEDICINE 16 (770). https://doi.org/10.1126/scitranslmed.adn2364.
Chicago author-date (all authors)
Declercq, Jozefien, Sarah Gerlo, Sharon Van Nevel, Natalie De Ruyck, Gabriële Holtappels, Liesbeth Delesie, Els Tobback, Inés Lammens, Nikita Gerebtsov, Koen Sedeyn, Xavier Saelens, Bart Lambrecht, Philippe Gevaert, Linos Vandekerckhove, and Stijn Vanhee. 2024. “Repeated COVID-19 MRNA-Based Vaccination Contributes to SARS-CoV-2 Neutralizing Antibody Responses in the Mucosa.” SCIENCE TRANSLATIONAL MEDICINE 16 (770). doi:10.1126/scitranslmed.adn2364.
Vancouver
1.
Declercq J, Gerlo S, Van Nevel S, De Ruyck N, Holtappels G, Delesie L, et al. Repeated COVID-19 mRNA-based vaccination contributes to SARS-CoV-2 neutralizing antibody responses in the mucosa. SCIENCE TRANSLATIONAL MEDICINE. 2024;16(770).
IEEE
[1]
J. Declercq et al., “Repeated COVID-19 mRNA-based vaccination contributes to SARS-CoV-2 neutralizing antibody responses in the mucosa,” SCIENCE TRANSLATIONAL MEDICINE, vol. 16, no. 770, 2024.
@article{01JDW7STJ0XEQK1RTTANR9WFKZ,
  abstract     = {{To prevent infection by respiratory viruses and consequently limit virus circulation, vaccines need to promote mucosal immunity. The extent to which the currently used messenger RNA (mRNA)-based COVID-19 vaccines induce mucosal immunity remains poorly characterized. We evaluated mucosal neutralizing antibody responses in a cohort of 183 individuals. Participants were sampled at several time points after primary adenovirus vector-based or mRNA-based COVID-19 vaccination and after mRNA-based booster vaccinations. Our findings revealed that repeated vaccination with mRNA boosters promoted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies in nasal secretions. Nasal and serum neutralizing antibody titers of both IgG and IgA isotypes correlated to one another. We investigated the source of these mucosal antibodies in a mouse model wherein mice received repeated mRNA vaccines for SARS-CoV-2. These experiments indicated that neutralizing antibody-producing cells reside in the spleen and bone marrow, whereas no proof of tissue homing to the respiratory mucosa was observed, despite the detection of mucosal antibodies. Serum transfer experiments confirmed that circulating antibodies were able to migrate to the respiratory mucosa. Collectively, these results demonstrate that, especially upon repeated vaccination, the currently used COVID-19 mRNA vaccines can elicit mucosal neutralizing antibodies and that vaccination might also stimulate mucosal immunity induced by previous SARS-CoV-2 infection. Moreover, migration of circulating antibodies to the respiratory mucosa might be a main mechanism. These findings advance our understanding of mRNA vaccine-induced immunity and have implications for the design of vaccine strategies to combat respiratory infections.}},
  articleno    = {{eadn2364}},
  author       = {{Declercq, Jozefien and Gerlo, Sarah and Van Nevel, Sharon and De Ruyck, Natalie and Holtappels, Gabriële and Delesie, Liesbeth and Tobback, Els and Lammens, Inés and Gerebtsov, Nikita and Sedeyn, Koen and Saelens, Xavier and Lambrecht, Bart and Gevaert, Philippe and Vandekerckhove, Linos and Vanhee, Stijn}},
  issn         = {{1946-6234}},
  journal      = {{SCIENCE TRANSLATIONAL MEDICINE}},
  keywords     = {{J-CHAIN,INDUCTION,IMMUNITY,CELLS}},
  language     = {{eng}},
  number       = {{770}},
  pages        = {{13}},
  title        = {{Repeated COVID-19 mRNA-based vaccination contributes to SARS-CoV-2 neutralizing antibody responses in the mucosa}},
  url          = {{http://doi.org/10.1126/scitranslmed.adn2364}},
  volume       = {{16}},
  year         = {{2024}},
}

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