Hybrid immunity from bivalent vaccination and prior infection enhances humoral and innate protection against Omicron XBB.1.16 and EG.5.1.1 variants in Japan

To investigate the role of hybrid immunity in enhancing humoral and innate immune responses against Omicron variants XBB.1.16 and EG.5.1.1.

Study Design: Analyzed samples from a case-control study of 50 breakthrough infection cases and 50 controls, all adults with ≥3 mRNA vaccine doses, during the XBB.1.5 wave in Japan.
Participant Classification: Participants were classified into hybrid immunity, high-vaccine-induced immunity, and low-vaccine-induced immunity groups based on prior infection and antibody levels.
Neutralization and Cytokine Analysis: Measured neutralization titers against SARS-CoV-2 variants and analyzed cytokines in serum and cell-based assays.

Breakthrough cases were more common in the low-vaccine-induced immunity group.
Hybrid immunity resulted in higher neutralization titers compared to vaccine-only groups.
Elevated IL-8 levels were observed in hybrid non-breakthrough participants.

The study was limited to a specific population in Japan and may not be generalizable.
The sample size was relatively small, which could affect the robustness of the findings.