Humoral and cellular immune responses following BNT162b2 XBB.1.5 vaccination

SARS-CoV-2 Omicron XBB subvariants efficiently evade immunity from prior infection or vaccination, requiring vaccine adaptation. Here, we analyzed immunogenicity of an adapted vaccine, BNT162b2 Omicron XBB.1.5, which is currently used for booster vaccination. Booster vaccination significantly increased anti-Spike IgG, accompanied by expansion of cross-reactive memory B cells recognizing Wuhan and Omicron XBB.1.5 spike variants. Geometric mean neutralizing titers against XBB.1.5, XBB.1.16 and XBB.2.3, as well as cross-reactive responses against EG.5.1 and BA.2.86 increased significantly relative to pre-booster titers. Finally, the number of Wuhan and XBB.1.5 spike reactive IFN-γ-producing T cells significantly increased after booster vaccination. In summary, BNT162b2 Omicron XBB.1.5 vaccination resulted in potent neutralizing antibody responses against Omicron XBB variants, including the recent Omicron variants EG.5.1 (Eris) and BA.2.86 (Pirola), as well as XBB.1.5 reactive T cell responses, suggesting that booster vaccination will augment protection against these emerging variants. ### Competing Interest Statement M.H., A.K., and S.P. conducted contract research (testing of vaccinee sera for neutralizing activity against SARS-CoV-2) for Valneva unrelated to this work. G.M.N.B. served as advisor for Moderna, S.P. served as advisor for BioNTech, unrelated to this work, A.D-J served as an advisor for Pfizer unrelated to this work. T.W. served as an advisor for Pfizer and received honoraria for seminars from Pfizer, both activities are unrelated to this work. The other authors declare no competing interests. ### Funding Statement G.M.N.B. and A.D.-J. acknowledge funding (Niedersaechsisches Ministerium fuer Wissenschaft und Kultur; 14-76103-184, COFONI Network, project 4LZF23) and A.D.-J. acknowledge funding by European Social Fund (ZAM5-87006761). S.P. acknowledges funding by the EU project UNDINE (grant agreement number 101057100), the Ministry for Science and Culture of Lower Saxony (Niedersaechsisches Ministerium fuer Wissenschaft und Kultur; 14-76103-184, COFONI Network, projects 7FF22, 6FF22, 10FF22) and the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG; PO 716/11-1). T.W. acknowledges funded by the DFG under Germany's Excellence Strategy EXC 2155 RESIST (Project 390874280). Research in the Foerster laboratory gets supported by the German Center for Infection Research TTU 01.938 (grant no 80018019238), by the German Center for Lung Research (grant 82DZL002B1), by the State of Lower Saxony (14-76103-184 CORONA-11/20), by DFG under Germany's Excellence Strategy EXC 2155 RESIST (Project ID39087428), SFB 900/3 (Project B1, 158989968) and FO334/7-1 (all to R.F.). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The analysis conducted for this article were approved by the Internal Review Board of Hannover Medical School (institutional review board no. 8973\_BO-K\_2020, last amendment Sep 2023). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data generated in this study are provided as a Source Data files in conjunction to this manuscript. All requests for raw and analyzed data that underlie the results reported in this article will be reviewed within four weeks by the CoCo Study Team, Hannover Medical School (cocostudie{at}mh-hannover.de) to determine whether the request is subject to confidentiality and data protection obligations. Data that can be shared will be released via a material transfer agreement.