1. SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2
- Author
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Ania Wajnberg, Willemijn Rijnink, Juan Manuel Carreño, Daniel C. Adelsberg, Giulio Kleiner, Carolina Bermúdez-González, Aaron J. Schmitz, Goran Bajic, Kayla T. Russo, Florian Krammer, Lubbertus C. F. Mulder, Levy A. Sominsky, Denise Jurczyszak, Fatima Amanat, Katherine Beach, Ashley Beathrese T. Salimbangon, Julia C. Matthews, Shaza M. Sayed Ahmed, Emilia Mia Sordillo, Shirin Strohmeier, Komal Srivastava, Mahima Thapa, Tinting Lei, Miti Saksena, Wanni A. Mendez, Deena R. Altman, Harm van Bakel, Lily Q. Eaker, Daniel L. Floda, Jackson S. Turner, Charles R Gleason, Shelcie Fabre, Sarah Zafar, Sayahi Suthakaran, Mahmoud Awawda, Rachel Chernet, Bulbul Ahmed, Viviana Simon, Ali H. Ellebedy, Julian Q. Zhou, Angela Amoako, Ana Gonzalez Reiche, Jose Polanco, Emily D. Ferreri, Hala Alshammary, Amber S. Shin, and Nicholas Borcherding
- Subjects
COVID-19 Vaccines ,Protein domain ,medicine.disease_cause ,Antibodies, Viral ,Binding, Competitive ,Article ,General Biochemistry, Genetics and Molecular Biology ,Immunoglobulin G ,03 medical and health sciences ,0302 clinical medicine ,Protein Domains ,medicine ,Humans ,RNA, Messenger ,030304 developmental biology ,0303 health sciences ,Messenger RNA ,Mutation ,biology ,SARS-CoV-2 ,Vaccination ,Antibodies, Monoclonal ,Virology ,Antibodies, Neutralizing ,Amino Acid Substitution ,Polyclonal antibodies ,Monoclonal ,Antibody Formation ,Spike Glycoprotein, Coronavirus ,biology.protein ,Angiotensin-Converting Enzyme 2 ,Somatic Hypermutation, Immunoglobulin ,Antibody ,030217 neurology & neurosurgery - 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 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., An analysis of mRNA vaccine-induced polyclonal antibodies and plasmablast derived monoclonal antibodies from individuals vaccinated against SARS-CoV-2 identifies a high proportion of non-neutralizing antibodies, the induction of cross-reactive antibodies to seasonal coronaviruses and also maps the regions in the spike protein that are targeted, even among viral variants.
- Published
- 2021