@article{02fd855f4d1f429aa58021625dd7e798,
title = "SARS-CoV-2 booster vaccination rescues attenuated IgG1 memory B cell response in primary antibody deficiency patients",
abstract = "Background: Although SARS-CoV-2 vaccines have proven effective in eliciting a protective immune response in healthy individuals, their ability to induce a durable immune response in immunocompromised individuals remains poorly understood. Primary antibody deficiency (PAD) syndromes are among the most common primary immunodeficiency disorders in adults and are characterized by hypogammaglobulinemia and impaired ability to mount robust antibody responses following infection or vaccination. Methods: Here, we present an analysis of both the B and T cell response in a prospective cohort of 30 individuals with PAD up to 150 days following initial COVID-19 vaccination and 150 days post mRNA booster vaccination. Results: After the primary vaccination series, many of the individuals with PAD syndromes mounted SARS-CoV-2 specific memory B and CD4+ T cell responses that overall were comparable to healthy individuals. Nonetheless, individuals with PAD syndromes had reduced IgG1+ and CD11c+ memory B cell responses following the primary vaccination series, with the defect in IgG1 class-switching rescued following mRNA booster doses. Boosting also elicited an increase in the SARS-CoV-2-specific B and T cell response and the development of Omicron-specific memory B cells in COVID-19-na{\"i}ve PAD patients. Individuals that lacked detectable B cell responses following primary vaccination did not benefit from booster vaccination. Conclusion: Together, these data indicate that SARS-CoV-2 vaccines elicit memory B and T cells in most PAD patients and highlights the importance of booster vaccination in immunodeficient individuals.",
keywords = "B cells, SARS-CoV-2, common variable immunodeficiency, hypogammaglobulinemia, immune memory, primary antibody deficiency, specific antibody deficiency, vaccination",
author = "Lin, {Frank J.} and Doss, {Alexa Michelle Altman} and Davis-Adams, {Hannah G.} and Adams, {Lucas J.} and Hanson, {Christopher H.} and VanBlargan, {Laura A.} and Liang, {Chieh Yu} and Chen, {Rita E.} and Monroy, {Jennifer Marie} and Wedner, {H. James} and Anthony Kulczycki and Mantia, {Tarisa L.} and O{\textquoteright}Shaughnessy, {Caitlin C.} and Saravanan Raju and Zhao, {Fang R.} and Elise Rizzi and Rigell, {Christopher J.} and Dy, {Tiffany Biason} and Kau, {Andrew L.} and Zhen Ren and Turner, {Jackson S.} and O{\textquoteright}Halloran, {Jane A.} and Presti, {Rachel M.} and Fremont, {Daved H.} and Kendall, {Peggy L.} and Ellebedy, {Ali H.} and Mudd, {Philip A.} and Diamond, {Michael S.} and Ofer Zimmerman and Laidlaw, {Brian J.}",
note = "Funding Information: MD is a consultant for Inbios, Vir Biotechnology, Senda Biosciences, Moderna, and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Moderna, Vir Biotechnology, Immunome, and Emergent BioSolutions. OZ and family own Moderna stock. The Ellebedy laboratory received unrelated funding support from Emergent BioSolutions and AbbVie. AE is a consultant for Mubadala Investment Company and the founder of ImmuneBio Consulting. JT is a consultant for Gerson Lehrman Group. JT and AE are recipients of a licensing agreement with Abbvie that is unrelated to this manuscript. Funding Information: This study utilized samples obtained from the Washington University School of Medicine COVID-19 biorepository, which is supported by the NIH/National Center for Advancing Translational Sciences (UL1 TR002345). The authors thank Likui Yang and the Bursky Center for Human Immunology Tetramer Core for their help generating tetramer reagents. The authors also express their gratitude to all study participants. Funding Information: This work was supported by grants and contracts from NIH: DP2AI169978 and K22AI153015 [all to BL], R01 AI157155, U01 AI151810, and 75N93019C00051 [all to MD], U01AI141990, U01AI150747, HHSN272201400006C, HHSN272201400008C, and 75N93019C00051 [all to AE], and R01 DK084242 [to PK]. The study also was supported by a VA Merit Award BX002882 [to PK]. Acknowledgments Publisher Copyright: Copyright {\textcopyright} 2022 Lin, Doss, Davis-Adams, Adams, Hanson, VanBlargan, Liang, Chen, Monroy, Wedner, Kulczycki, Mantia, O{\textquoteright}Shaughnessy, Raju, Zhao, Rizzi, Rigell, Dy, Kau, Ren, Turner, O{\textquoteright}Halloran, Presti, Fremont, Kendall, Ellebedy, Mudd, Diamond, Zimmerman and Laidlaw.",
year = "2022",
month = dec,
day = "22",
doi = "10.3389/fimmu.2022.1033770",
language = "English",
volume = "13",
journal = "Frontiers in Immunology",
issn = "1664-3224",
}