SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared to SARS-CoV-2 mRNA vaccinations

 Elizabeth M. Anderson, Theresa Eiloa, Eileen Goodwin, Marcus J. Bolton, Sigrid Gouma, Rishi R. Goel, Mark M Painter, Sokratis A. Apostolidis, Divij Mathew, Debora Dunbar, Danielle Fiore, Amanda Brock, JoEllen Weaver, John S. Millar, Stephanie DerOhannessian, The UPenn COVID Processing Unit, Allison R. Greenplate, Ian Frank, Daniel J Rader, E John Wherry,  

View ORCID ProfileScott E. Hensley

doi: https://doi.org/10.1101/2021.09.30.21264363

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.09.30.21264363v1.full.pdf

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines elicit higher levels of antibodies compared to natural SARS-CoV-2 infections in most individuals; however, the specificities of antibodies elicited by vaccination versus infection remain incompletely understood. Here, we characterized the magnitude and specificity of SARS-CoV-2 spike-reactive antibodies from 10 acutely infected health care workers and 23 participants who received mRNA-based SARS-CoV-2 vaccines. We found that infection and primary mRNA vaccination elicited S1 and S2-reactive antibodies, while secondary vaccination boosted mostly S1 antibodies. Using magnetic bead-based absorption assays, we found that SARS-CoV-2 infections elicited a large proportion of original antigenic sin-like antibodies (from first exposure to infective) that bound efficiently to common seasonal human coronaviruses but poorly to SARS-CoV-2. In converse, vaccination only modestly boosted antibodies reactive to common seasonal human coronaviruses and these antibodies bound efficiently to SARS-CoV-2. Our data indicate that SARS-CoV-2 mRNA vaccinations elicit fundamentally different antibody responses compared to SARS-CoV-2 infections.

Competing Interest Statement

E.J.W. has consulting agreements with and/or is on the scientific advisory board for Merck, Elstar, Janssen, Related Sciences, Synthekine and Surface Oncology. E.J.W. is a founder of Surface Oncology and Arsenal Biosciences. E.J.W. is an inventor on a patent (U.S. patent number 10,370,446) submitted by Emory University that covers the use of PD-1 blockade to treat infections and cancer. S.E.H. has received consultancy fee from Sanofi Pasteur, Lumen, Novavax, and Merck for work unrelated to this report.

Clinical Trial

n/a, study was completed with de-identified samples from a separate study

Funding Statement

This project has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93021C00015. This work was supported in part by institutional funds from the University of Pennsylvania and NIH U19AI082630 (S.E.H. and E.J.W.). E.M.A. was supported by the NIH Training in Virology T32 Program (T32-AI-007324). We thank J. Lurie, J. Embiid, J. Harris, and D. Blitzer for philanthropic support. We thank all members of the Penn COVID-19 Sample Processing Unit. We would like to thank David Anderson for assistance with the graphical abstract. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

https://www.medrxiv.org/content/10.1101/2021.09.30.21264363v1