Cellular and humoral immunity following two AZD1222 and two booster vaccinations in hemodialysis patients

Background: Dialysis patients are vulnerable to SARS-CoV-2 infection and subsequent complications. However, the vaccine-induced immunity, especially against new variants, following two AZD1222 and two booster doses in hemodialysis patients remain largely unknown. Methods: In this observational cohort study, we monitored immune responses in 127 hemodialysis patients receiving the 3^rd and 4th vaccinations until three months after the 4th immunization. Humoral and cellular immunity were assessed by anti-SARS-CoV-2 receptor-binding domain(RBD) antibody, neutralizing antibodies against the ancestral virus, delta, omicron BA.1 and BA.2 and SARS-CoV-2 specific IFN-γ releasing assay (Covi-FERON). Results: The primary series and the fourth dose predominantly consisted of two-dose AZD1222 and mRNA-1273, respectively. The most common vaccines chosen for the third dose was mRNA-1273(n = 84), following by BNT 162b2(n = 38). Anti-RBD antibody increased to 13803.8 and 18197U/ml after the 3^rd and 4th vaccination, respectively, but dropped to 8709.6U/ml three months after the fourth vaccination. One month after the fourth vaccination, 99 %,98 %,51.5 % and 93.9 % participants had neutralizing antibodies against the ancestral virus, delta, omicron BA.1 and BA.2, respectively. 87.9 % and 81.8 % patients reacted to the ancestral or alpha and beta or gamma spike antigens in Covi-FERON, respectively, after four vaccinations. Higher Covi-FERON reactions were associated with increased IL-2 and IL-4 secretion. In linear mixed effect models, mRNA-1273 as the third vaccination was associated higher anti-RBD antibody titers and higher neutralization against the ancestral virus and delta compared with BNT162b2 but with higher mild adverse events following vaccination. Conclusions: Two AZD1222 and two mRNA booster doses confer substantial humoral and cellular immunity against variants including omicron in hemodialysis patients.