Safety and Immunogenicity After Primary and Booster Inactivated SARS-Cov-2 Vaccination in Patients with Autoimmune Liver Diseases

Background and Aims:SARS-CoV-2 vaccines-associated autoimmune liver diseases have been reported in several case reports.However,the safety and immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in patients with autoimmune liver diseases(AILD)is still unknown.Methods:Eighty-four patients with AILD were prospectively followed up after the second dose(primary)of inactivated SARS-CoV-2 vaccine.Some of them received the third dose(booster)of inactivated vaccine.Adverse events(AEs),autoimmune activation,and liver inflammation exacerbation after primary and booster vaccination were recorded.Meanwhile,dynamics of antireceptor-binding-domain IgG(anti-RBD-IgG),neutralizing antibodies(NAbs)and RBD-specific B cells responses were evaluated.Results:The overall AEs in AILD patients after primary and booster vaccination were 26.2%and 13.3%,respectively.The decrease of C3 level and increase of immunoglobulin light chain K andλlevels were observed in AILD patients after primary vaccination,however,liver inflammation was not exacerbated,even after booster vaccination.Both the seroprevalence and titers of anti-RBD-IgG and NAbs were decreased over time in AILD patients after primary vaccination.Notably,the antibody titers were significantly elevated after booster vaccination(10-fold in anti-RBD-IgG and 7.4-fold in NAbs,respectively),which was as high as in healthy controls.Unfortunately,the inferior antibody response was not enhanced after booster vaccination in patients with immunosuppressants.Changes of atypical memory B cells were inversely related to antibody levels,which indicate that the impaired immune memory was partially restored partly by the booster vaccination.Conclusions:The well tolerability and enhanced humoral immune response of inactivated vaccine supports an additional booster vaccination in AILD patients without immunosuppressants.

Dynamic Humoral Immune Response to Primary and Booster Inactivated SARS-CoV-2 Vaccination in Patients with Cirrhosis

Background and Aims:Our aim was to determine the immune efficacy of a severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)booster vaccination in cirrhotic patients who had received the primary series.Methods:We performed a longitudinal assessment in 48 patients with cirrhosis,57 patients with chronic hepatitis B(CHB)and 68 healthy controls(HCs)to continuously track the dynamics of SARS-CoV-2 specific antibodies and memory B cells after receiving the primary series and booster dose at different times.A pseudovirus neutralization assay was used to determine neutralization against Omicron subvariants BA.2.12.1,BA.4 and BA.5 from serum samples collected from three cohorts.Results:Serum anti-receptor-binding domain(RBD)immunoglobulin(Ig)G and neutralizing antibody(NAb)levels in cirrhotic patients were elevated within 15–45 days after completing the primary series before rapidly declining and reaching a valley at around 165–195 days.After receiving the booster dose,both antibody levels were significantly increased to levels comparable to patients with CHB and HCs.Subgroup analysis showed that booster vaccination induced weaker antibody responses in patients with decompensated cirrhosis than in those with compensated cirrhosis.The SARS-CoV-2 memory B-cell response in cirrhotic patients was durable during follow-up regardless of the hepatic fibrocirrhosis grade.However,compared with the primary series,the booster dose did not result in an evident improvement of neutralization activity against the Omicron subvariants BA.2.12.1 and BA.4,and was followed by a significant decrease in the titer against BA.5.Conclusions:A booster dose elicited a robust and durable humoral response to the wild-type strain in cirrhotic patients but not the Omicron subvariants.Repeated vaccination of inactivated SARS-CoV-2 vaccine may not benefit cirrhotic patients in neutralization against newly circulating strains.