SARS-CoV-2 infection and vaccination elicit distinct pharyngeal mucosal B cell responses in children

Kalpana Manthiram; Qin Xu; Lihong Shi; Liya Wang; Foo Cheung; Aparna Kotekar; Galina Koroleva; Elizabeth Rice; Richard Apps; Justin Lack; Craig Martens; Iyadh Douagi; Can Liu; Juraj Kabat; Hengameh Behzadpour; Lela Kardava; Tovah Markowitz; Margery Smelkinson; Kenneth Hoehn; Clarisa Buckner; Dominic Golec; Lorenza Bellusci; Gabrielle Grubbs; Sara Pourhashemi; Juanjie Tang; Asya Khleborodova; Martha Kirby; Rachel Sparks; Andrew Martins; John Tsang; Susan Moir; Surender Khurana; Pamela Mudd; Pamela Schwartzberg

doi:10.21203/rs.3.rs-7428491/v1

SARS-CoV-2 infection and vaccination elicit distinct pharyngeal mucosal B cell responses in children

Res Sq [Preprint]. 2025 Sep 9:rs.3.rs-7428491. doi: 10.21203/rs.3.rs-7428491/v1.

Authors

Kalpana Manthiram¹, Qin Xu¹, Lihong Shi², Liya Wang², Foo Cheung³, Aparna Kotekar², Galina Koroleva¹, Elizabeth Rice², Richard Apps⁴, Justin Lack², Craig Martens⁵, Iyadh Douagi⁵, Can Liu⁶, Juraj Kabat⁷, Hengameh Behzadpour⁸, Lela Kardava⁹, Tovah Markowitz¹⁰, Margery Smelkinson¹¹, Kenneth Hoehn¹², Clarisa Buckner⁷, Dominic Golec², Lorenza Bellusci¹³, Gabrielle Grubbs¹³, Sara Pourhashemi¹³, Juanjie Tang¹⁴, Asya Khleborodova², Martha Kirby¹⁵, Rachel Sparks², Andrew Martins¹⁶, John Tsang¹⁶, Susan Moir¹⁷, Surender Khurana¹³, Pamela Mudd⁸, Pamela Schwartzberg¹

Affiliations

¹ NIAID/National Institutes of Health.
² National Institute of Allergy and Infectious Diseases.
³ Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI).
⁴ University of Cambridge.
⁵ NIH.
⁶ Yale School of Medicine.
⁷ National Institutes of Health.
⁸ Children's National Hospital.
⁹ National Institute of Allergy & Infectious Disease.
¹⁰ NIAID, NIH.
¹¹ NIAID.
¹² Department of Biomedical Data Science, Geisel School of Medicine at Darmouth, Hanover, NH, United States.
¹³ Food and Drug Administration.
¹⁴ CBER/Food and Drug Administration.
¹⁵ National Human Genome Research Institute.
¹⁶ Yale University.
¹⁷ Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Abstract

Mucosal immunity is an important correlate of protection against respiratory infections such as SARS-CoV-2. Comparing B cell responses in the upper respiratory tract following vaccination and infection may offer unique insights into mucosal immunity. Here, we characterized antigen-specific B cells in the tonsils, adenoids, and peripheral blood of children who had been infected with SARS-CoV-2 or vaccinated with SARS-CoV-2 mRNA vaccines. SARS-CoV-2-specific switched memory B cells (B_SM) and germinal center B cells were found in the blood and pharyngeal lymphoid tissues after vaccination or infection. However, infection generated a higher proportion of IgA⁺ B_SM and CXCR3⁺CD21⁺ B_SM, which showed distinct spatial localization, greater clonal expansion and increased propensity for plasma cell differentiation compared to their CXCR3^- counterparts, accompanied by persistent activation of innate and T follicular helper cells in the tissues. Our data provide evidence for tissue-specific B cell memory after either SARS-CoV-2 vaccination or infection, but with distinct characteristics that can influence the quality, durability, and localization of immunity.

Publication types

Preprint

Grants and funding

R00 AI159302/AI/NIAID NIH HHS/United States