Antibody‐dependent NK‐cell and neutralizing antibody responses against the Spike protein of Wuhan‐Hu‐1 and Omicron BA.1 SARS‐CoV‐2 variants in vaccinated experienced and vaccinated naïve individuals

Abstract

AbstractAntibodies triggering Fc‐mediated NK cell activity may contribute to protection against disease caused by SARS‐CoV‐2 infection in humans. However, how these Fc‐mediated humoral responses compare between individuals displaying hybrid immunity (Vac‐ex) and those fully vaccinated with no history of SARS‐CoV‐2 infection (Vac‐n) and whether they correlate with neutralizing antibody (NtAb) responses remains largely undetermined. In this retrospective study serum samples from 50 individuals (median age, 44.5 years; range, 11–85; 25 males), 25 Vac‐ex and 25 Vac‐n were studied. A flow‐cytometry‐based antibody‐mediated NK‐cell activation assay was used to quantitate effector NK‐cells stimulated to express LAMP1 (lysosomal associated membrane protein 1), MIP1 (Macrophage inflammatory protein 1), and interferon‐γ (IFNγ); NK cells isolated from two donors (D1 and D2) were used. NtAb levels targeting the Spike protein of Wuhan‐Hu‐1 and Omicron BA.1 SARS‐CoV‐2 variants were quantitated using a SARS‐CoV‐2 S pseudotyped neutralization assay. Regardless of the SARS‐CoV‐2 variant S antigen used in the NK‐cell activation assay, the frequency of NK cells stimulated to express LAMP‐1, MIP1β, and IFNγ was higher in Vac‐ex compared with Vac‐n (p values ranging from 0.07 to 0.006) for D1; this was only seen for BA.1 when NK cells from D2 were employed. The frequency of functional NK cells activated by antibody binding to either Wuhan‐Hu‐1 or Omicron BA.1 S protein was not significantly different for both VAC‐ex and VAC‐n. In contrast, NtAb titers against BA.1 were around 10‐fold lower than that against Wuhan‐Hu‐1. Vac‐ex displayed higher NtAb titers against both (sub)variants than Vac‐n. NK‐cell responses correlated poorly with NtAb titers (ρ ≤ 0.30). The data demonstrate higher cross‐reactivity across variants of concern for antibodies triggering Fc‐mediated NK cell than for NtAb. Moreover, Vac‐Ex seemed to display more robust functional antibody responses as compared with Vac‐n.