Humoral and Cellular Immunity following Bivalent mRNA Boosters in Patients on Hemodialysis

Background: Dialysis patients are at high risk of SARS-CoV-2 related morbidity and mortality. Although bivalent vaccines targeting Omicron subvariants were recommended, data on the immunogenicity in the hemodialysis (HD) population remain limited. Methods: In this prospective observational study, we enrolled patients on maintenance HD scheduled to receive bivalent mRNA vaccines. Immune responses were assessed before, and one and three months after vaccination (baseline, M1 and M3), and also at M1 and M3 after breakthrough infection. Age-matched healthy adults served as controls. Humoral immunity outcomes included anti-SARS-CoV-2-S antibody, surrogate viral neutralization tests (sVNT) against the ancestral virus, Omicron BA.1, BA.2 and BA.4/5, and pseudovirus neutralization tests against Omicron BF.7, B.2.75, BQ.1.1 and XBB.1.5. Cellular immunity was evaluated with interferon-γ release assay (IGRA) targeting spike proteins from various variants. Results: A total of 106 HD patients (median age 66) received Spikevax Original/Omicron BA.1 (89.6%) or BA.4-5 (10.4%) from October 2022 to February 2023. Of these, 25.5% had prior infection, and 93.4% had received four doses of vaccines including two AZD1222 and two mRNA vaccines. Anti-SARS-CoV-2-S antibody levels increased by 4.2-fold and subsequently halved at M3. sVNT showed increased neutralization against Omicron subvariants peaked at M1 and positive rates remained high(75.3~96%) at M3. Pseudovirus neutralizing capacity against Omicron BF.7, B.2.75, BQ.1.1 and XBB.1.5 increased by 2-to-9.9 times. However, only 58.1% of patients showed a positive IGRA response at M1, with no correlation to humoral outcomes. No significant differences in humoral and cellular immunity were demonstrated between HD patients and health controls. In those with 5 immunizations, Anti-SARS-CoV-2-S antibody and sVNT against BA.4/5 at M3 were higher following hybrid immunity than pure vaccinations. In multivariate linear mixed effect model, previous SARS-CoV2 infection attenuated neutralization against the ancestral virus. Conclusion: Bivalent mRNA vaccines boosted antibody titers and broaden neutralization against new Omicron subvariants in HD patients. However, cellular immunity was suboptimal despite multiple immunizations including bivalent vaccines and infection, highlighting a potential area for further investigation. Funding: Government Support – Non-U.S.