@article{2064e0b005cc436080147ef5f9b45b66,
title = "High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy",
abstract = "Peanut allergy can result in life-threatening reactions and is a major public health concern. Oral immunotherapy (OIT) induces desensitization to food allergens through administration of increasing amounts of allergen. To dissect peanut-specific immunoglobulin E (IgE) and IgG responses in subjects undergoing OIT, we have developed AllerScan, a method that leverages phage-display and next-generation sequencing to identify the epitope targets of peanut-specific antibodies. We observe a striking diversification and boosting of the peanut-specific IgG repertoire after OIT and a reduction in pre-existing IgE levels against individual epitopes. High-resolution epitope mapping reveals shared recognition of public epitopes in Ara h 1, 2, 3, and 7. In individual subjects, OIT-induced IgG specificities overlap extensively with IgE and exhibit strikingly similar antibody footprints, suggesting related clonal lineages or convergent evolution of peanut-specific IgE and IgG B cells. Individual differences in epitope recognition identified via AllerScan could inform safer and more effective personalized immunotherapy.",
keywords = "IgE, allergen immunotherapy, antibody, antibody repertoire, epitope mapping, food allergy, high-throughput sequencing, oral immunotherapy, peanut allergy, phage display",
author = "Genghao Chen and Shrock, {Ellen L.} and Li, {Mamie Z.} and Spergel, {Jonathan M.} and Nadeau, {Kari C.} and Pongracic, {Jacqueline A.} and Umetsu, {Dale T.} and Rima Rachid and MacGinnitie, {Andrew J.} and Wanda Phipatanakul and Lynda Schneider and Oettgen, {Hans C.} and Elledge, {Stephen J.}",
note = "Funding Information: S.J.E. is a co-founder of TSCAN Therapeutics, MAZE Therapeutics, ImmuneID, and Mirimus. S.J.E. serves on the Scientific Advisory Board (SAB) of CRISPR Therapeutics; Homology Medicines, Inc.; TSCAN Therapeutics; and X-Chem and is an advisor for MPM. S.J.E. and G.C. have applied for a patent on these findings. J.M.S. has received research funding from Aimmune Therapeutics, Regeneron, Sanofi, Novartis, and FARE. K.C.N. is co-founder of IgGenix, Latitude, Alladapt, and BeforeBrands. She also serves on the SAB or Data and Safety Monitoring Boards (DSMB) of Novartis, Regeneron, ClostraBio, Cour Pharmaceuticals, Aravax, and NHLBI. D.T.U. and H.C.O. serve on the SAB of IgGenix. J.A.P. is on the Independent Data Monitoring Committee of Regeneron and Clinical Advisory Board of FARE and has served as an investigator for Aimmune Therapeutics and FARE. She has received research funding from DBV, FARE, The Sunshine Charitable Foundation, and Peak6 Investments LLC. A.J.M. is an advisor to DBV Technologies. R.R. has received research funding from Aimmune Therapeutics. W.P. is a consultant for Genentech, Novartis, Regeneron, and Sanofi and received research support from Thermo Fisher Scientific. L.S. serves on the Medical Advisory Board for Food Allergy Research and Education and the DSMB for Alladapt and is an investigator for DBV Technologies and Regeneron. None of these affiliations represent a conflict of interest with respect to the design or execution of this study or interpretation of data presented in this manuscript. Funding Information: We thank A. Kohlgruber for comments on the manuscript. H.C.O. was supported by NIH grant 2R01AI119918-06 and the Food Allergy Science Initiative . K.C.N. received support from R01AI140134-02 , 5UM2AI130836-04 , 5U19 AI104209-07 , and 5U01 AI140498-03 . D.T.U. was funded by the Bunning Food Allergy Initiative . W.P. was supported by NIH U01 AI126614 and U01 AI126614 . The PRROTECT study was funded by FARE , the Bunning Food Allergy Initiative , and Genentech . The study was conducted with support from Harvard Catalyst/Harvard Clinical and Translational Science Center ( National Center for Research Resources and the National Center for Advancing Translational Sciences , National Institutes of Health award UL1 TR001102 ) and financial contributions from Harvard University and its affiliated academic health care centers. E.L.S. is funded by the NSF Graduate Research Fellowship Program. S.J.E. is an Investigator with the Howard Hughes Medical Institute. Funding Information: We thank A. Kohlgruber for comments on the manuscript. H.C.O. was supported by NIH grant 2R01AI119918-06 and the Food Allergy Science Initiative. K.C.N. received support from R01AI140134-02, 5UM2AI130836-04, 5U19 AI104209-07, and 5U01 AI140498-03. D.T.U. was funded by the Bunning Food Allergy Initiative. W.P. was supported by NIH U01 AI126614 and U01 AI126614. The PRROTECT study was funded by FARE, the Bunning Food Allergy Initiative, and Genentech. The study was conducted with support from Harvard Catalyst/Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic health care centers. E.L.S. is funded by the NSF Graduate Research Fellowship Program. S.J.E. is an Investigator with the Howard Hughes Medical Institute. G.C. E.L.S. H.C.O. and S.J.E. designed the study. E.L.S. designed the peanut AllerScan library. M.Z.L. cloned and packaged the peanut AllerScan library. G.C. performed AllerScan experiments and data analysis, with input from E.L.S. H.C.O. and S.J.E. J.M.S. K.C.N. J.A.P. D.T.U. R.R. A.J.M. and L.S. conducted the PRROTECT clinical trial under the direction of L.S. and provided sera used in this study. W.P. provided sera from children without food allergy. J.M.S. K.C.N. J.A.P. D.T.U. R.R. A.J.M. L.S. W.P. and H.C.O. contributed to the interpretation of data from a clinical perspective. G.C. E.L.S. H.C.O. and S.J.E. wrote the manuscript, with input and editing by all authors. S.J.E. is a co-founder of TSCAN Therapeutics, MAZE Therapeutics, ImmuneID, and Mirimus. S.J.E. serves on the Scientific Advisory Board (SAB) of CRISPR Therapeutics; Homology Medicines, Inc.; TSCAN Therapeutics; and X-Chem and is an advisor for MPM. S.J.E. and G.C. have applied for a patent on these findings. J.M.S. has received research funding from Aimmune Therapeutics, Regeneron, Sanofi, Novartis, and FARE. K.C.N. is co-founder of IgGenix, Latitude, Alladapt, and BeforeBrands. She also serves on the SAB or Data and Safety Monitoring Boards (DSMB) of Novartis, Regeneron, ClostraBio, Cour Pharmaceuticals, Aravax, and NHLBI. D.T.U. and H.C.O. serve on the SAB of IgGenix. J.A.P. is on the Independent Data Monitoring Committee of Regeneron and Clinical Advisory Board of FARE and has served as an investigator for Aimmune Therapeutics and FARE. She has received research funding from DBV, FARE, The Sunshine Charitable Foundation, and Peak6 Investments LLC. A.J.M. is an advisor to DBV Technologies. R.R. has received research funding from Aimmune Therapeutics. W.P. is a consultant for Genentech, Novartis, Regeneron, and Sanofi and received research support from Thermo Fisher Scientific. L.S. serves on the Medical Advisory Board for Food Allergy Research and Education and the DSMB for Alladapt and is an investigator for DBV Technologies and Regeneron. None of these affiliations represent a conflict of interest with respect to the design or execution of this study or interpretation of data presented in this manuscript. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = oct,
day = "19",
doi = "10.1016/j.xcrm.2021.100410",
language = "English (US)",
volume = "2",
journal = "Cell Reports Medicine",
issn = "2666-3791",
publisher = "Cell Press",
number = "10",
}
