@article{321a22736d7247dda789b0224d69a21b,
title = "SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2",
abstract = "In this study we profiled vaccine-induced polyclonal antibodies as well as plasmablast-derived mAbs from individuals who received SARS-CoV-2 spike mRNA vaccine. Polyclonal antibody responses in vaccinees were robust and comparable to or exceeded those seen after natural infection. However, the ratio of binding to neutralizing antibodies after vaccination was greater than that after natural infection and, at the monoclonal level, we found that the majority of vaccine-induced antibodies did not have neutralizing activity. We also found a co-dominance of mAbs targeting the NTD and RBD of SARS-CoV-2 spike and an original antigenic-sin like backboost to spikes of seasonal human coronaviruses OC43 and HKU1. Neutralizing activity of NTD mAbs but not RBD mAbs against a clinical viral isolate carrying E484K as well as extensive changes in the NTD was abolished, suggesting that a proportion of vaccine-induced RBD binding antibodies may provide substantial protection against viral variants carrying single E484K RBD mutations.",
keywords = "NTD, RBD, SARS-CoV-2, mAbs, mRNA vaccination, plasmablasts, spike",
author = "{The Personalized Virology Initiative} and Fatima Amanat and Mahima Thapa and Tinting Lei and Ahmed, {Shaza M.Sayed} and Adelsberg, {Daniel C.} and Carre{\~n}o, {Juan Manuel} and Shirin Strohmeier and Schmitz, {Aaron J.} and Sarah Zafar and Zhou, {Julian Q.} and Willemijn Rijnink and Hala Alshammary and Nicholas Borcherding and Reiche, {Ana Gonzalez} and Komal Srivastava and Sordillo, {Emilia Mia} and {van Bakel}, Harm and Bulbul Ahmed and Deena Altman and Angela Amoako and Mahmoud Awawda and Katherine Beach and Carolina Berm{\'u}dez-Gonz{\'a}lez and Rachel Chernet and Lily Eaker and Shelcie Fabre and Ferreri, {Emily D.} and Daniel Floda and Charles Gleason and Giulio Kleiner and Denise Jurczyszak and Julia Matthews and Wanni Mendez and Mulder, {Lubbertus C.F.} and Jose Polanco and Kayla Russo and Ashley Salimbangon and Miti Saksena and Shin, {Amber S.} and Levy Sominsky and Sayahi Suthakaran and Ania Wajnberg and Turner, {Jackson S.} and Goran Bajic and Viviana Simon and Ellebedy, {Ali H.} and Florian Krammer",
note = "Funding Information: We would like to thank Dr. Randy A. Albrecht for oversight of the conventional BSL3 biocontainment facility, which makes our work with live SARS-CoV-2 possible. We are also grateful for Mount Sinai{\textquoteright}s leadership during the COVID-19 pandemic. We want to especially thank Drs. Peter Palese, Carlos Cordon-Cardo, Dennis Charney, David Reich, and Kenneth Davis for their support. We would also like to thank Bassem Mohamed and Wooseob Kim for their help with preparing the scRNA-seq libraries. This work was partially funded by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051 , NIAID Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C and HHSN272201400006C ), NIAID grants U01AI141990 and U01AI150747 , by the generous support of the JPB Foundation and the Open Philanthropy Project (research grant 2020-215611) (5384 ); and by anonymous donors. J.S.T. was supported by NIAID 5T32CA009547 . Funding Information: We would like to thank the study participants for their generosity and willingness to participate in longitudinal COVID-19 research studies. None of this work would be possible without their contributions. We would like to thank Dr. Randy A. Albrecht for oversight of the conventional BSL3 biocontainment facility, which makes our work with live SARS-CoV-2 possible. We are also grateful for Mount Sinai's leadership during the COVID-19 pandemic. We want to especially thank Drs. Peter Palese, Carlos Cordon-Cardo, Dennis Charney, David Reich, and Kenneth Davis for their support. We would also like to thank Bassem Mohamed and Wooseob Kim for their help with preparing the scRNA-seq libraries. This work was partially funded by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051, NIAID Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C and HHSN272201400006C), NIAID grants U01AI141990 and U01AI150747, by the generous support of the JPB Foundation and the Open Philanthropy Project (research grant 2020-215611) (5384); and by anonymous donors. J.S.T. was supported by NIAID 5T32CA009547. F.A. G.B. V.S. A.H.E. and F.K. developed the concept. H.A. K.S. The Personalized Virology Initiative, and V.S. recruited patients, collected and processed biospecimen, and cultured primary viral isolates from participants. M.T. T.L. S.M.S.A. A.J.S. and J.S.T. performed the antibody isolation. J.Q.Z. B.N. and A.H.E. performed the B cell sequence analysis. A.G.R. H.v.B. and E.M.S. acquired samples and sequenced viruses. F.A. J.M.C. S.S. S.Z. and W.R. characterized sera and mAbs and created reagents. D.C.A. measured affinities. F.A. G.B. V.S. A.H.E. and F.K. analyzed the data. G.B. V.S. A.H.E. and F.K. created the figures. F.K. wrote the manuscript. F.A. G.B. V.S. and A.H.E. edited the manuscript. All authors read, subedited, and approved the manuscript. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines which list F.K. as co-inventor. V.S. and F.A. are also listed on the serological assay patent application as a co-inventors. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. F.K. has consulted for Merck and Pfizer (before 2020) and is currently consulting for Pfizer, Seqirus, and Avimex. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2. A.H.E. has consulted for InBios and Fimbrion Therapeutics (before 2021) and is currently a consultant for Mubadala Investment Company. The Ellebedy laboratory received funding under sponsored research agreements that are unrelated to the data presented in the current study from Emergent BioSolutions and from AbbVie. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = jul,
day = "22",
doi = "10.1016/j.cell.2021.06.005",
language = "English",
volume = "184",
pages = "3936--3948.e10",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "15",
}