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
Masayuki Amano, Sachiko Otsu, Yukari Uemura, Yasuko Ichikawa, Shota Matsumoto, Nobuyo Higashi‐Kuwata, Shuzo Matsushita, Shinya Shimada, Hiroaki Mitsuya
Abstract
Abstract 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.