Potent induction of humoral and cellular immunity after bivalent BA.4/5 mRNA vaccination in dialysis patients with and without history of SARS-CoV-2 infection

Abstract

AbstractKnowledge on immunogenicity of the bivalent Omicron BA.4/5 vaccine in dialysis patients and the effect of a previous infection is limited. Therefore, vaccine-induced humoral and cellular immunity was analyzed in dialysis patients and immunocompetent controls with and without prior infection.In an observational study, 33 dialysis patients and 58 controls matched for age, sex and prior infection status were recruited. Specific IgG, neutralizing antibody activity and cellular immunity towards the spike-antigen from parental SARS-CoV-2 and Omicron subvariants BA.1, BA.2 and BA.4/5 were analyzed before and 13-18 days after vaccination.The bivalent vaccine led to a significant induction of IgG, neutralizing titers, and specific CD4 and CD8 T-cell levels. Neutralizing activity towards the parental strain was highest, whereas specific T-cell levels towards parental spike and Omicron subvariants did not differ indicating substantial cross-reactivity. Dialysis patients with prior infection had significantly higher spike-specific CD4 T-cell levels with lower CTLA-4 expression compared to infection-naïve patients. When compared to controls, no differences were observed between individuals without prior infection. Among infected individuals, CD4 T-cell levels were higher in dialysis patients and neutralizing antibodies were higher in controls. Vaccination was overall well tolerated in both dialysis patients and controls with significantly less adverse events among dialysis patients.In conclusion, our study did not provide any evidence for impaired immunogenicity of the bivalent Omicron BA.4/5 vaccine in dialysis patients. Unlike in controls, previous infection of patients was even associated with higher levels of spike-specific CD4 T cells, which may reflect prolonged encounter with antigen during infection.Translational statementDialysis patients with uremic immunodeficiency are at increased risk for infectious complications after SARS-CoV-2 infection and have been shown to insufficiently respond towards the first doses of COVID-19 vaccines. Bivalent vaccines are now recommended, although knowledge on immunogenicity and on the effect of a previous infection is limited in this patient group. We show that the bivalent BA.4/5 vaccine was well tolerated and led to a pronounced induction of antibodies, neutralizing antibodies and T cells, which was overall similar in magnitude in non-infected patients and controls. Despite some differences between patients and controls with prior infection, our data do not provide any evidence towards impaired immunity in dialysis patients.