Discussion and conclusion
The increase of neutralizing antibodies following the administration of the bivalent booster we documented in our study (i.e., 7.0–fold increase) was consistent with the conclusions of other studies4,7. As for the humoral response following the first two doses of BNT162b2 and the homologous booster 8,9, a substantial waning of the humoral response was observed 6 months after the administration of the BNT162b2 bivalent booster. This decrease was especially important considering the XBB.1.5 subvariant. Moreover, the drop of neutralizing antibodies over time coincides with the decrease of bivalent booster effectiveness against infection in the recent report of Lin et al. 10.
A significant decay in the cellular response was also observed over time. Nevertheless, the proportion of samples still able to generate IFNγ in response to an in vitro SARS-CoV-2 stimulation remained high. This observation is consistent with the maintained and superior effectiveness against severe disease in the report of Lin et al.10. The fact that the release of IFNγ could represent a good surrogate of the risk of severe infection still remains to be evaluated. Importantly, these data can also help national competent authorities in their recommendation regarding the administration of an additional booster.