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Distinct features of SARS-CoV-2 humoral immunity against Omicron breakthrough infection

•Humoral immunity after SARS-CoV-2 Omicron breakthrough infections (BTI) was characterized using neutralizing and variant-specific antibody measurements.•Omicron-BTI patients showed robust neutralizing activity to all the WT, Delta, and Omicron strains in the convalescent phase.•The humoral characte...

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Published in:Vaccine 2023-11, Vol.41 (47), p.7019-7025
Main Authors: Goto, Takeyuki, Chong, Yong, Tani, Naoki, Susai, Natsumi, Yoshinaga, Tomoyo, Sasaki, Tomoki, Taniguchi, Masahiro, Kusakabe, Takahiro, Shimono, Nobuyuki, Akashi, Koichi, Ikematsu, Hideyuki
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Language:English
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Summary:•Humoral immunity after SARS-CoV-2 Omicron breakthrough infections (BTI) was characterized using neutralizing and variant-specific antibody measurements.•Omicron-BTI patients showed robust neutralizing activity to all the WT, Delta, and Omicron strains in the convalescent phase.•The humoral characteristics of Omicron-BTI patients were between unvaccinated Omicron patients and uninfected vaccinees.•Our study suggests that cross-reactive vaccine-induced immunity was intensively stimulated after Omicron-BTI, which contributed to Omicron neutralization.•Measuring SARS-CoV-2 variant-specific antibody levels, as well as neutralizing activity, is useful for evaluating humoral immunity after breakthrough infection. SARS-CoV-2 Omicron breakthrough infection (Omicron-BTI) after vaccination has been frequently observed. A more detailed understanding of the humoral immunity against Omicron-BTI is required. We measured strain-specific live-virus based neutralizing activity, anti-spike IgG, and anti-receptor-binding domain (RBD) IgG titers in individuals with Omicron/BA.1-BTI and directly compared them with controls with diverse combinations of wild-type (WT) mRNA vaccination and infection history. Omicron-BTI individuals showed markedly higher neutralizing titers against all the WT, Delta, and Omicron strains in convalescent sera, compared with unvaccinated Omicron-infection individuals with only Omicron neutralizing activity. Similar tendencies were found in strain-specific anti-spike and anti-RBD IgG titers. The Omicron-specificity (BA.1/WT neutralizing ratio), Omicron-neutralizing efficiency per antibody unit, and anti-Omicron RBD-directivity of anti-spike antibodies in Omicron-BTI individuals were all significantly lower than those in unvaccinated Omicron-infection individuals, but they were equivalent to or higher than those in uninfected vaccinees. The induction of Omicron-specific neutralizing activity after Omicron-BTI was not weakened for eight months from the last vaccination. These findings suggest that cross-reactive vaccine-induced immunity was intensively stimulated following Omicron breakthrough infection, which contributed to Omicron neutralization. Measuring SARS-CoV-2 variant-specific antibody levels as well as neutralizing activity is useful for evaluating humoral immunity after breakthrough infection in the current situation of antigenic gaps between vaccinated and epidemic (Omicron sub-lineages) strains.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2023.10.035