SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity

Jillian R. Jaycox, Carolina Lucas, Inci Yildirim, Yile Dai, Eric Y. Wang, Valter Monteiro, Sandra Lord, Jeffrey Carlin, Mariko Kita, Jane H. Buckner, Shuangge Ma, Melissa Campbell, Albert Ko, Saad Omer, Carrie L. Lucas, Cate Speake (), Akiko Iwasaki () and Aaron M. Ring ()
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Jillian R. Jaycox: Yale School of Medicine
Carolina Lucas: Yale School of Medicine
Inci Yildirim: Yale University School of Medicine
Yile Dai: Yale School of Medicine
Eric Y. Wang: Yale School of Medicine
Valter Monteiro: Yale School of Medicine
Sandra Lord: Benaroya Research Institute at Virginia Mason
Jeffrey Carlin: Virginia Mason Medical Center
Mariko Kita: Virginia Mason Medical Center
Jane H. Buckner: Benaroya Research Institute at Virginia Mason
Shuangge Ma: Yale School of Public Health
Melissa Campbell: Yale University School of Medicine
Albert Ko: Yale University School of Medicine
Saad Omer: Yale University
Carrie L. Lucas: Yale School of Medicine
Cate Speake: Benaroya Research Institute at Virginia Mason
Akiko Iwasaki: Yale School of Medicine
Aaron M. Ring: Yale School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-9

Abstract: Abstract mRNA-based vaccines dramatically reduce the occurrence and severity of COVID-19, but are associated with rare vaccine-related adverse effects. These toxicities, coupled with observations that SARS-CoV-2 infection is associated with autoantibody development, raise questions whether COVID-19 vaccines may also promote the development of autoantibodies, particularly in autoimmune patients. Here we used Rapid Extracellular Antigen Profiling to characterize self- and viral-directed humoral responses after SARS-CoV-2 mRNA vaccination in 145 healthy individuals, 38 patients with autoimmune diseases, and 8 patients with mRNA vaccine-associated myocarditis. We confirm that most individuals generated robust virus-specific antibody responses post vaccination, but that the quality of this response is impaired in autoimmune patients on certain modes of immunosuppression. Autoantibody dynamics are remarkably stable in all vaccinated patients compared to COVID-19 patients that exhibit an increased prevalence of new autoantibody reactivities. Patients with vaccine-associated myocarditis do not have increased autoantibody reactivities relative to controls. In summary, our findings indicate that mRNA vaccines decouple SARS-CoV-2 immunity from autoantibody responses observed during acute COVID-19.

Date: 2023
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DOI: 10.1038/s41467-023-36686-8

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