LAUSR

The humoral immune response against severe acute respiratory syndrome coronavirus 2 (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) postinfection 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 were significantly increased in Rec9m compared to Rec2m (p < 0.001). The neutralizing potency observed in Rec9m was consistently higher than in Rec2m against variants of concern (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 messenger RNA‐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.