mRNA vaccines induce more spike-specific antibody isotypes with more binding capacity than natural infection

 Jéromine Klingler, Gregory S. Lambert, Vincenza Itri, Sean Liu, Juan C. Bandres, Gospel Enyindah-Asonye, Xiaomei Liu,  

View ORCID ProfileKasopefoluwa Y. Oguntuyo, Fatima Amanat, Benhur Lee, Susan Zolla-Pazner, Chitra Upadhyay, Catarina E. Hioe

doi: https://doi.org/10.1101/2021.05.11.21256972

This article is a preprint and has not been peer-reviewed [what does this mean?].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/10.1101/2021.05.11.21256972v1.full.pdf

Abstract

Background Mass vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is on-going in the United States with vaccines approved for emergency use by the FDA. Each vaccine can induce spike-specific antibodies (Abs) with virus-neutralizing activities; however, the Fc-mediated Ab activities have received little attention. Moreover, while plasma/serum Abs are commonly studied, scant information is available about Abs in the respiratory mucosa, the site of SARS-CoV-2 transmission.

Methods Plasma and saliva were collected from mRNA vaccine recipients and convalescent coronavirus disease 2019 (COVID-19) patients. Antigen-specific total Ig and Ig isotypes were measured. In addition to virus neutralization, Fc-mediated activities were investigated, including antibody-dependent cellular phagocytosis (ADCP) and complement deposition.

Results Similar to infection, vaccination stimulated spike-specific Ab responses detected in plasma and saliva, with IgG1 as the dominant isotype. Interestingly, vaccination produced greater IgG2, IgG3, and IgG4 responses and higher ratios of (IgG1+IgG3)/(IgG2+IgG4) than infection. Moreover, while plasma neutralization and ADCP potencies were comparable in vaccinated and convalescent individuals, vaccine-induced plasma Abs elicited stronger complement binding and activation.

Conclusion Compared with natural infection, mRNA vaccines induced a greater array of IgG subtypes against spike in saliva and plasma. The vaccine-induced Abs were also more potent in mediating complement activation.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This work was supported in part by the Department of Medicine of the Icahn School of Medicine at Mount Sinai Department of Medicine (to S.Z-P., C.E.H.); the Department of Microbiology and the Ward-Coleman estate for endowing the Ward-Coleman Chairs at the Icahn School of Medicine at Mount Sinai (to B.L.), the Department of Veterans Affairs [Merit Review Grant I01BX003860] (to C.E.H.) and [Research Career Scientist Award 1IK6BX004607] (to C.E.H.); the National Institutes of Health [grant AI139290] to C.E.H., [grants R01 AI123449, R21 AI1498033] to B.L, [grant R01 AI140909] to C.U. G.E-A and K.Y.O. were supported by Viral-Host Pathogenesis Training Grant T32 AI07647. K.Y.O was also supported by Training Grant F31 AI154739.

https://www.medrxiv.org/content/10.1101/2021.05.11.21256972v1