SARS-CoV-2 mRNA vaccines induce a greater array of spike-specific antibody isotypes with more potent complement binding capacity than natural infection

Klingler, Jéromine; Lambert, Gregory S.; Itri, Vincenza; Liu, Sean; Bandres, Juan C.; Enyindah-Asonye, Gospel; Liu, Xiaomei; Oguntuyo, Kasopefoluwa Y.; Amanat, Fatima; Lee, Benhur; Zolla-Pazner, Susan; Upadhyay, Chitra; Hioe, Catarina E.

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.