Longer intervals between SARS-CoV-2 infection and mRNA-1273 doses improve the neutralization of different variants of concern.

The humoral immune response against SARS-CoV-2 variants of concern elicited by vaccination was evaluated in COVID-19 recovered individuals (Rec) separated 1-3 months (Rec2m) or 4-12 months (Rec9m) post infection and compared to the response in naïve participants. Antibody-mediated immune responses were assessed in 66 participants by three commercial immunoassays and a SARS-CoV-2 lentiviral-based pseudovirus neutralization assay. Immunoglobulin (Ig) levels against SARS-CoV-2 spike were lower in naïve participants after two doses than in Rec after a single dose (p<0.05). After two doses in Rec, levels of total Ig to receptor binding domain (RBD) were significantly increased in Rec9m compared to Rec2m (p<0.001). The neutralizing potency observed in Rec9m was consistently higher than in Rec2m against VOCs Alpha, Beta, Delta, and BA.1 sublineage of Omicron with 2.2-2.8-fold increases. Increasing the interval between SARS-CoV-2 infection and the vaccination with mRNA-based vaccines to more than 3 months generates a more efficient heterologous humoral immune response against VOCs by allowing enough time to mount a strong recall memory B cell response. This article is protected by copyright. All rights reserved.