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Abstract Background Patients with end stage renal disease (ESRD) undergoing hemodialysis are at increased risk for infection and impaired vaccination responses. We analyzed overlap and influencing factors of vaccination responses against severe acute respiratory syndrome corona virus disease 2 (SARS-CoV-2) and Hepatitis B virus (HBV). Methods SARS-CoV-2 and HBV vaccination response was assessed in a cohort of German ESRD hemodialysis patients. Anti-HBs- and SARS-CoV-2 anti-S-IgG were analyzed by ELISA. Demographic and clinical data were extracted from clinical files. Results Sixty-four patients with complete information on HBV and SARS-CoV-2 vaccination responses were included. More than one-third (35.4%) of non-responders upon HBV vaccination were identified. Unresponsiveness after HBV and poor response after SARS-CoV-2 vaccination showed strong overlap, and overall, 70.3% of patients were classified into concordant HBV/SARS vaccination response groups. HBV vaccination non-responsiveness, but not poor SARS-CoV-2 post-vaccination immunity was associated with obesity, while poor SARS-CoV-2 vaccination responses were associated increased age. Conclusion Our findings confirm previous reports on impaired vaccination response in hemodialysis patients and show that post-vaccination humoral responses against SARS-CoV-2 and HBV display strong overlap in this vulnerable patient group. These results may help to adapt vaccination strategies in this highly vulnerable population. Trial registration: German Clinical Trial Registry, DRKS00021152.

Abstract The recently detected Omicron BA.2.86 lineage contains more than 30 amino acid mutations relative to BA.2. BA.2.86 and its JN.1 derivative evade neutralization by serum antibodies of fully vaccinated individuals. In this study, we elucidate epitopes driving the immune escape of BA.2.86 and JN.1 via pseudovirus neutralization. Here we generate 33 BA.2.86 mutants, each reverting a single mutation back to BA.2. We use this library in an approach that we call reverse mutational scanning to define distinct neutralization titers against each epitope. Mutations within the receptor binding domain at K356T, V483Δ, and to a lesser extent N460K, A484K, and F486P enhance immune escape. Interestingly, 16insMPLF within the spike N-terminal domain and P621S within S1/S2 also significantly contribute to antibody escape of BA.2.86. Upon XBB.1.5 booster vaccination, neutralization titers against JN.1 and BA.2.86 improve considerably, and residual immune escape is driven by 16insMPLF, N460K, E554K, and to a lesser extent P621S, and A484K.