Comparison of immune responses to SARS-CoV-2 spike following Omicron infection or Omicron BA.4/5 vaccination in kidney transplant recipients.

Background: The emergence of novel SARS-CoV-2 variants challenges immunity, particularly among immunocompromised kidney transplant recipients (KTRs). To address this, vaccines have been adjusted to circulating variants. Despite intensive vaccination efforts, SARS-CoV-2 infections surged among KTRs during the Omicron wave, enabling a direct comparison of variant-specific immunity following-vaccination against Omicron BA.4/5 or Omicron infection in KTRs.
Methods: 98 SARS-CoV-2 naïve KTRs who had received four vaccine doses were studied. Before and after a 5th antigen exposure, either via the bivalent vaccine composed of ancestral SARS-CoV-2 and Omicron BA.4/5 (29 KTRs) or via natural infection with Omicron (38 BA.4/5, 31 BA.1/2), spike-specific T cells were quantified using Elispot and serum pseudovirus neutralizing activity was assessed against the ancestral Wuhan strain, BA.5 and XBB.1.5.
Results: Compared to BA.4/5 vaccination, spike-specific T-cell responses and neutralization activity were higher up to six months post-Omicron infection and reached levels similar to healthy controls. Vaccinated KTRs showed modestly boosted neutralization activity against the Wuhan strain and BA.5, but not XBB.1.5. Baseline immunity correlated with immune responses three months post-vaccination and post-infection, indicating a predictive value for peak immune responses. Tixagevimab/Cilgavimab treatment was associated with robust neutralization of the Wuhan strain, but ineffective against XBB.1.5.
Conclusion: The BA.4/5 vaccine improved neutralizing activity against the BA.4/5 variant, but not against the subsequently circulating XBB.1.5 variant in KTRs. Conversely, omicron infection boosted T cells and humoral responses more effectively, showing efficacy against XBB.1.5. These findings suggest that infection-induced immunity associates with greater protection than vaccination against future variants in KTRs.
Competing Interests: HG and FK are inventors on patent applications on SARS-CoV-2 neutralizing antibodies filed by the University of Cologne and have received payments from the University of Cologne for licensed antibodies. LK received consulting fees or payment/honoraria from ViiV, Theratechnologies, Gilead and MSD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2025 Tometten, Brandt, Schlotz, Stumpf, Landmann, Kantauskaite, Lamberti, Hillebrandt, Müller, Kittel, Ivens, Gruell, Voges, Schaal, Lübke, Königshausen, Rump, Klein, Stegbauer and Timm.)