@article{19f968ae7d514160a2dceb556597e85a,
title = "mRNA vaccine boosting enhances antibody responses against SARS-CoV-2 Omicron variant in individuals with antibody deficiency syndromes",
abstract = "Individuals with primary antibody deficiency (PAD) syndromes have poor humoral immune responses requiring immunoglobulin replacement therapy. We followed individuals with PAD after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination by evaluating their immunoglobulin replacement products and serum for anti-spike binding, Fcγ receptor (FcγR) binding, and neutralizing activities. The immunoglobulin replacement products tested have low anti-spike and receptor-binding domain (RBD) titers and neutralizing activity. In coronavirus disease 2019 (COVID-19)-naive individuals with PAD, anti-spike and RBD titers increase after mRNA vaccination but wane by 90 days. Those vaccinated after SARS-CoV-2 infection develop higher and more sustained responses comparable with healthy donors. Most vaccinated individuals with PAD have serum-neutralizing antibody titers above an estimated correlate of protection against ancestral SARS-CoV-2 and Delta virus but not against Omicron virus, although this is improved by boosting. Thus, some immunoglobulin replacement products likely have limited protective activity, and immunization and boosting of individuals with PAD with mRNA vaccines should confer at least short-term immunity against SARS-CoV-2 variants, including Omicron.",
keywords = "COVID-19, SARS-CoV-2, combined variable antibody deficiency, hypogammaglobulinemia, immune response, mRNA vaccine, neutralization, specific antibody deficiency, vaccine",
author = "Ofer Zimmerman and {Altman Doss}, {Alexa Michelle} and Paulina Kaplonek and Liang, {Chieh Yu} and VanBlargan, {Laura A.} and Chen, {Rita E.} and Monroy, {Jennifer Marie} and Wedner, {H. James} and Anthony Kulczycki and Mantia, {Tarisa L.} and O'Shaughnessy, {Caitlin C.} and Davis-Adams, {Hannah G.} and Bertera, {Harry L.} and Adams, {Lucas J.} and Saravanan Raju and Zhao, {Fang R.} and Christopher Rigell and Dy, {Tiffany Biason} and Kau, {Andrew L.} and Zhen Ren and Turner, {Jackson S.} and O'Halloran, {Jane A.} and Presti, {Rachel M.} and Fremont, {Daved H.} and Kendall, {Peggy L.} and Ellebedy, {Ali H.} and Galit Alter and Diamond, {Michael S.}",
note = "Funding Information: This study was supported by grants and contracts from the NIH (R01 AI157155, U01 AI151810, and 75N93019C00051 to M.S.D.; U01AI141990, U01AI150747, HHSN272201400006C, HHSN272201400008C, and 75N93019C00051 to A.H.E.; and R01 DK084242 to P.L.K.). The study was also supported by a VA Merit Award (BX002882 to P.L.K.). 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 WU353 and WU368 studies were reviewed and approved by the Washington University Institutional Review Board (approval nos. 202003186 and 202012081, respectively). The authors also express their gratitude to all study participants. O.Z. designed the study, wrote the study protocol, performed experiments, analyzed the data, and supervised the project. A.M.A.D. enrolled subjects, collected demographic and clinical data, performed experiments, and analyzed data. L.A.V. C.-Y.L. and R.E.C. designed and performed neutralization experiments and analyzed data. P.K. and H.L.B. performed Luminex profiling and analyzed data. H.J.W. A.K. Jr. T.B.D. A.L.K. and Z.R. provided patient care. T.L.M. wrote the study protocol, managed institutional review board compliance, enrolled individuals, and processed samples. J.M.M. C.C.O. and C.J.R. collected demographic and clinical data, enrolled individuals, and processed samples. H.G.D.-A. performed SARS ELISA CoV-2 spike and RBD protein expression experiments. L.J.A. and D.H.F. generated crucial reagents. S.R. planned experiments and analyzed data. F.R.Z. contributed to the design of the study and analyzed data. A.H.E. and J.S.T. contributed samples from the healthy donor cohort. J.A.O. and R.M.P. wrote and maintained the institutional review board protocol, recruited and phlebotomized participants, and coordinated sample collection of healthy donors. P.L.K. contributed to supervision of the project. G.A. designed experiments and analyzed data. M.S.D. planned experiments and analyzed data. O.Z. and M.S.D. wrote the initial draft with detailed comments from A.M.A.D. All other authors provided editorial comments after the first draft. M.S.D. is a consultant for Inbios, Vir Biotechnology, Senda Biosciences, and Carnival Corporation and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Moderna, Vir Biotechnology, Immunome, and Emergent BioSolutions. O.Z. and family own Moderna stock. G.A. is a founder and equity holder for Seromyx Systems Inc. and an equity holder for Leyden Labs. The Ellebedy laboratory received unrelated funding support from Emergent BioSolutions and AbbVie. A.H.E. is a consultant for Mubadala Investment Company and the founder of ImmuneBio Consulting. J.S.T. is a consultant for Gerson Lehrman Group. J.S.T. and A.H.E. are recipients of a licensing agreement with Abbvie that is unrelated to this manuscript. Funding Information: M.S.D. is a consultant for Inbios, Vir Biotechnology, Senda Biosciences, and Carnival Corporation and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Moderna, Vir Biotechnology, Immunome, and Emergent BioSolutions. O.Z. and family own Moderna stock. G.A. is a founder and equity holder for Seromyx Systems Inc. and an equity holder for Leyden Labs. The Ellebedy laboratory received unrelated funding support from Emergent BioSolutions and AbbVie. A.H.E. is a consultant for Mubadala Investment Company and the founder of ImmuneBio Consulting. J.S.T. is a consultant for Gerson Lehrman Group. J.S.T. and A.H.E. are recipients of a licensing agreement with Abbvie that is unrelated to this manuscript. Funding Information: This study was supported by grants and contracts from the NIH ( R01 AI157155 , U01 AI151810 , and 75N93019C00051 to M.S.D.; U01AI141990 , U01AI150747 , HHSN272201400006C , HHSN272201400008C , and 75N93019C00051 to A.H.E.; and R01 DK084242 to P.L.K.). The study was also supported by a VA Merit Award ( BX002882 to P.L.K.). 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 WU353 and WU368 studies were reviewed and approved by the Washington University Institutional Review Board (approval nos. 202003186 and 202012081, respectively). The authors also express their gratitude to all study participants. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = jun,
day = "21",
doi = "10.1016/j.xcrm.2022.100653",
language = "English",
volume = "3",
journal = "Cell Reports Medicine",
issn = "2666-3791",
number = "6",
}