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The plasmablast response to SARS-CoV-2 mRNA vaccination is dominated by non-neutralizing antibodies that target both the NTD and the RBD

Fatima Amanat; Mahima Thapa; Tingting Lei; Shaza M. Sayed Ahmed; Daniel C. Adelsberg; Juan Manuel Carreno; Shirin Strohmeier; Aaron J. Schmitz; Sarah Zafar; Julian Q Zhou; Willemijn Rijnink; Hala Alshammary; Nicholas Borcherding; Ana Gonzalez Reiche; Komal Srivastava; Emilia Mia Sordillo; Harm van Bakel; Jackson S. Turner; Goran Bajic; Viviana M Simon; Ali H. Ellebedy; Florian Krammer.
Preprint en Inglés | PREPRINT-MEDRXIV | ID: ppmedrxiv-21253098
In this study we profiled vaccine-induced polyclonal antibodies as well as plasmablast derived mAbs from subjects 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, that 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 spike proteins. 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 E484K.