TY - JOUR
T1 - SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2
AU - The Personalized Virology Initiative
AU - Amanat, Fatima
AU - Thapa, Mahima
AU - Lei, Tinting
AU - Ahmed, Shaza M.Sayed
AU - Adelsberg, Daniel C.
AU - Carreño, Juan Manuel
AU - Strohmeier, Shirin
AU - Schmitz, Aaron J.
AU - Zafar, Sarah
AU - Zhou, Julian Q.
AU - Rijnink, Willemijn
AU - Alshammary, Hala
AU - Borcherding, Nicholas
AU - Reiche, Ana Gonzalez
AU - Srivastava, Komal
AU - Sordillo, Emilia Mia
AU - van Bakel, Harm
AU - Ahmed, Bulbul
AU - Altman, Deena
AU - Amoako, Angela
AU - Awawda, Mahmoud
AU - Beach, Katherine
AU - Bermúdez-González, Carolina
AU - Chernet, Rachel
AU - Eaker, Lily
AU - Fabre, Shelcie
AU - Ferreri, Emily D.
AU - Floda, Daniel
AU - Gleason, Charles
AU - Kleiner, Giulio
AU - Jurczyszak, Denise
AU - Matthews, Julia
AU - Mendez, Wanni
AU - Mulder, Lubbertus C.F.
AU - Polanco, Jose
AU - Russo, Kayla
AU - Salimbangon, Ashley
AU - Saksena, Miti
AU - Shin, Amber S.
AU - Sominsky, Levy
AU - Suthakaran, Sayahi
AU - Wajnberg, Ania
AU - Turner, Jackson S.
AU - Bajic, Goran
AU - Simon, Viviana
AU - Ellebedy, Ali H.
AU - Krammer, Florian
N1 - 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’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:
© 2021 Elsevier Inc.
PY - 2021/7/22
Y1 - 2021/7/22
N2 - 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.
AB - 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.
KW - NTD
KW - RBD
KW - SARS-CoV-2
KW - mAbs
KW - mRNA vaccination
KW - plasmablasts
KW - spike
UR - http://www.scopus.com/inward/record.url?scp=85108943246&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2021.06.005
DO - 10.1016/j.cell.2021.06.005
M3 - Article
C2 - 34192529
AN - SCOPUS:85108943246
VL - 184
SP - 3936-3948.e10
JO - Cell
JF - Cell
SN - 0092-8674
IS - 15
ER -