Neutralization against Omicron sublineages (BA.2/BA.5/BQ.1.1/XBB/XBB.1.5) in bivalent BNT162b2-vaccinated HCWs with or without risk factors, or following BT infection with Omicron

SARS-CoV-2-BA.4/5-adapted-bivalent-BNT162b2-vaccine ((bv)BNT), developed in response to the recent emergence of immune-evasive Omicron-variants, has been given to individuals who completed at least 2-doses of the monovalent-BNT162b2-vaccine ((mv)BNT). In the present cohort study, we evaluated neutralization-titers (NT(50)s) against Wuhan-strain (SCoV2(Wuhan)) and Omicron-sublineages including BA.2/BA.5/BQ.1.1/XBB/XBB.1.5, and vaccine-elicited S1-binding-IgG in sera from participants-vaccinated with 5th-(bv)BNT following 4th-(mv)BNT. The 5th-(bv)BNT-dose elicited good protective-activity against SCoV2(Wuhan) with geometric-mean (gMean)-NT(50) of 1966–2091, higher than the peak-values post-4th-(mv)BNT with no statistical significance, and favorable neutralization-activity against not only BA.5 but also BA.2, with ~ 3.2-/~ 2.2-fold greater gMean-NT(50) compared to the peak-values post-4th-(mv)BNT-dose, in participants with or without risk factors. However, neutralization-activity of sera post-5th-(bv)BNT-dose was low against BQ.1.1/XBB/XBB.1.5. Interestingly, participants receiving (bv)BNT following breakthrough (BT) infection during Omicron-wave had significantly enhanced neutralization-activity against SCoV2(Wuhan)/BA.2/BA.5 with ~ 4.6-/~ 6.3-/~ 8.1-fold greater gMean-NT(50), respectively, compared to uninfected participants receiving (bv)BNT. Sera from BT-infected-participants receiving (bv)BNT had enhanced neutralization-activity against BQ.1.1/XBB/XBB.1.5 by ~ 3.8-fold compared to those from the same participants post-4th-(mv)BNT-dose, and had enhanced gMean-NT(50) ~ 5.4-fold greater compared to those of uninfected-participants’ sera post-(bv)BNT. These results suggest that repeated stimulation brought about by exposure to BA.5’s-Spike elicit favorable cross-neutralization-activity against various SARS-CoV-2-variants.