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Distinct SARS-CoV-2 Antibody Responses Elicited by Natural Infection and mRNA Vaccination

Rafael Assis, Aarti Jain, Rie Nakajima, Al Jasinskas, Saahir Kahn, Anton Palma, View ORCID ProfileDaniel M. Parker, Anthony Chau, Amanda Leung, Christina Grabar, Fjolla Muqolli, Ghali Khalil, Jessica Colin Escobar, Jenny Ventura, D. Huw Davies, Bruce Albala, Bernadette Boden-Albala, Sebastian Schubl, Philip L. Felgner
doi: https://doi.org/10.1101/2021.04.15.440089
Rafael Assis
1University of California Irvine, School of Medicine and the Vaccine R&D Center
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Aarti Jain
1University of California Irvine, School of Medicine and the Vaccine R&D Center
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Rie Nakajima
1University of California Irvine, School of Medicine and the Vaccine R&D Center
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Al Jasinskas
1University of California Irvine, School of Medicine and the Vaccine R&D Center
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Saahir Kahn
2University of Southern California, Division of Infectious Diseases, Department of Medicine, Keck School of Medicine, Los Angeles, CA, USA
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Anton Palma
3University of California Irvine, Institute for Clinical & Translational Science
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Daniel M. Parker
4University of California Irvine, School of Medicine, Department of Neurology (BA, BBA) and Center for Clinical Research (BA)
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  • ORCID record for Daniel M. Parker
Anthony Chau
5University of California Irvine, Program in Public Health, Department of Health Society and Behavior (BBA), Department of Population Health Disease Prevention and Department of Epidemiology and Biostatistics (DP)
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Amanda Leung
6University of California Irvine, School of Medicine
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Christina Grabar
6University of California Irvine, School of Medicine
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Fjolla Muqolli
6University of California Irvine, School of Medicine
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Ghali Khalil
6University of California Irvine, School of Medicine
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Jessica Colin Escobar
6University of California Irvine, School of Medicine
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Jenny Ventura
6University of California Irvine, School of Medicine
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D. Huw Davies
1University of California Irvine, School of Medicine and the Vaccine R&D Center
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Bruce Albala
4University of California Irvine, School of Medicine, Department of Neurology (BA, BBA) and Center for Clinical Research (BA)
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Bernadette Boden-Albala
4University of California Irvine, School of Medicine, Department of Neurology (BA, BBA) and Center for Clinical Research (BA)
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Sebastian Schubl
6University of California Irvine, School of Medicine
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Philip L. Felgner
1University of California Irvine, School of Medicine and the Vaccine R&D Center
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  • For correspondence: pfelgner@hs.uci.edu
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Abstract

We analyzed data from two ongoing COVID-19 longitudinal serological surveys in Orange County, CA., between April 2020 and March 2021. A total of 8,476 finger stick blood specimens were collected before and after an aggressive mRNA vaccination campaign. IgG levels were determined using a multiplex antigen microarray containing 10 SARS-CoV-2 antigens, 4 SARS, 3 MERS, 12 Common CoV, and 8 Influenza antigens. Twenty-six percent of 3,347 specimens from unvaccinated Orange County residents in December 2020 were SARS-CoV-2 seropositive. The Ab response was predominantly against nucleocapsid (NP), full length spike and the spike S2 domain. Anti-receptor binding domain (RBD) reactivity was low and there was no cross-reactivity against SARS S1 or SARS RBD. An aggressive mRNA vaccination campaign at the UCI Medical Center started on December 16, 2020 and 6,724 healthcare workers were vaccinated within 3 weeks. Seroprevalence increased from 13% in December to 79% in January, 93% in February and 99% in March. mRNA vaccination induced much higher Ab levels especially against the RBD domain and significant cross-reactivity against SARS RBD and S1 was also observed. Nucleocapsid protein Abs can be used to distinguish individuals in a population of vaccinees to classify those who have been previously infected and those who have not, because nucleocapsid is not in the vaccine. Previously infected individuals developed higher Ab titers to the vaccine than those who have not been previously exposed. These results indicate that mRNA vaccination rapidly induces a much stronger and broader Ab response than SARS-CoV-2 infection.

Competing Interest Statement

The coronavirus antigen microarray is intellectual property of the Regents of the University of California that is licensed for commercialization to Nanommune Inc. (Irvine, CA), a private company for which Philip L. Felgner is the largest shareholder and several co-authors (Assis, Jain, Nakajima, Jasinskas, Davies, and Khan) also own shares. Nanommune Inc. has a business partnership with Sino Biological Inc. (Beijing, China) which expressed and purified the antigens used in this study, The other authors have no competing interests

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted May 19, 2021.
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Distinct SARS-CoV-2 Antibody Responses Elicited by Natural Infection and mRNA Vaccination
Rafael Assis, Aarti Jain, Rie Nakajima, Al Jasinskas, Saahir Kahn, Anton Palma, Daniel M. Parker, Anthony Chau, Amanda Leung, Christina Grabar, Fjolla Muqolli, Ghali Khalil, Jessica Colin Escobar, Jenny Ventura, D. Huw Davies, Bruce Albala, Bernadette Boden-Albala, Sebastian Schubl, Philip L. Felgner
bioRxiv 2021.04.15.440089; doi: https://doi.org/10.1101/2021.04.15.440089
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Distinct SARS-CoV-2 Antibody Responses Elicited by Natural Infection and mRNA Vaccination
Rafael Assis, Aarti Jain, Rie Nakajima, Al Jasinskas, Saahir Kahn, Anton Palma, Daniel M. Parker, Anthony Chau, Amanda Leung, Christina Grabar, Fjolla Muqolli, Ghali Khalil, Jessica Colin Escobar, Jenny Ventura, D. Huw Davies, Bruce Albala, Bernadette Boden-Albala, Sebastian Schubl, Philip L. Felgner
bioRxiv 2021.04.15.440089; doi: https://doi.org/10.1101/2021.04.15.440089

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