Protection of Omicron bivalent vaccine, previous infection, and their induced neutralizing antibodies against symptomatic infection with Omicron XBB.1.16 and EG.5.1

Background Data are limited on the protective role of the Omicron BA bivalent vaccine, previous infection, and their induced neutralizing antibodies against Omicron XBB.1.16 and EG.5.1 infection. Methods We conducted a nested case-control analysis among tertiary hospital staff in Tokyo who had received three or more doses of COVID-19 vaccines and donated blood samples in June 2023 (1 month before Omicron XBB.1.16 and EG.5.1 wave). We identified 206 symptomatic cases between June and September 2023 and selected their controls with 1:1 propensity-score matching. We examined the association of vaccination, previous infection, and preinfection live-virus neutralizing antibody titers against Omicron XBB.1.16 and EG.5.1 with the risk of COVID-19 infection. Results Previous infection during Omicron BA- or XBB-dominant phases was associated with a significantly lower infection risk during the XBB.1.16 and EG.5.1 dominant phase than infection-naïve with 70% and 100% protection, respectively, whereas Omicron BA bivalent vaccination showed no association. Preinfection-neutralizing titers against XBB.1.16 and EG.5.1 were 39% (95%CI: 8–60) and 28% (95%CI: 8–44), respectively, lower in cases than in matched controls. Neutralizing activity against XBB.1.16 and EG.5.1. were somewhat detectable in the sera of individuals with previous infection but barely detectable in those who were infection-naïve and received the Omicron bivalent vaccine. Conclusions In the era when the Omicron XBB vaccine was unavailable, the Omicron BA bivalent vaccine did not confer the neutralizing activity and protection against Omicron XBB.1.16 and EG.5.1 symptomatic infection. The previous infection afforded neutralizing titers and protection against symptomatic infection with these variants.