Unveiling unique effector function-related bulk antibody profiles in long-term hemodialysis patients following COVID-19 mRNA booster vaccination

Abstract

Background: Hemodialysis patients exhibit a reduced response to vaccination and have different vaccine dose regimens. Vaccines induce antibodies and affect the inflammatory balance through antibody glycosylation and effector functions. Therefore, we aimed to analyze the antibody glycosylation profiles in hemodialysis patients who were vaccinated against severe acute respiratory syndrome coronavirus 2, infected with the virus, or both, and compare them with those of dialysis patients in a control group. Methods: Plasma samples from 112 hemodialysis patients were assigned to four groups: control, infected, vaccinated, and post-vaccine-infected. Paired plasma samples from 47 people with vaccination (vaccinees) were analyzed before and after the booster dose. The same analytical approach was applied to the four groups for a cross-sectional comparison. Results: Our study found that both vaccination and infection groups showed decreased fucosylation of IgG1, which is associated with a proinflammatory biosignature. However, vaccination also leads to increased galactosylation and bisection of IgG antibodies, which are associated with anti-inflammatory effects and the additional regulation of immune responses. In contrast, infection led to an additional decrease in the fucosylation of IgG2 and IgA, demonstrating a more intense proinflammatory biosignature than vaccination. Conclusions: Our findings emphasize the proinflammatory biosignature of afucosylation in both vaccination and infection groups. Additionally, we uncovered further regulated profiles related to galactosylation in vaccinees. These findings suggest that antibody investigation for vaccination or infection should not solely focus on neutralization but should also consider effector function-related glycosylation profiling. This comprehensive information can be valuable for fine-tuning vaccine development in the future.