Factors associated with the humoral response after three doses of COVID-19 vaccination in kidney transplant recipients

Abstract

IntroductionKidney transplant recipients showed a weak humoral response to the mRNA COVID-19 vaccine despite receiving three cumulative doses of the vaccine. New approaches are still needed to raise protective immunity conferred by the vaccine administration within this group of high-risk patients. MethodsTo analyze the humoral response and identify any predictive factors within these patients, we designed a prospective monocentric longitudinal study of Kidney transplant recipients (KTR) who received three doses of mRNA-1273 COVID-19 vaccine. Specific antibody levels were measured by chemiluminescence. Parameters related to clinical status such as kidney function, immunosuppressive therapy, inflammatory status and thymic function were analyzed as potential predictors of the humoral response. ResultsSeventy-four KTR and sixteen healthy controls were included. One month after the administration of the third dose of the COVID-19 vaccine, 64.8% of KTR showed a positive humoral response. As predictive factors of seroconversion and specific antibody titer, we found that immunosuppressive therapy, worse kidney function, higher inflammatory status and age were related to a lower response in KTR while immune cell counts, thymosin-a1 plasma concentration and thymic output were related to a higher humoral response. Furthermore, baseline thymosin-a1 concentration was independently associated with the seroconversion after three vaccine doses. DiscussionIn addition to the immunosuppression therapy, condition of kidney function and age before vaccination, specific immune factors could also be relevant in light of optimization of the COVID-19 vaccination protocol in KTR. Therefore, thymosin-a1, an immunomodulatory hormone, deserves further research as a potential adjuvant for the next vaccine boosters.

Cell-mediated and Neutralizing Antibody Responses to the SARS-CoV-2 Omicron BA.4/BA.5–adapted Bivalent Vaccine Booster in Kidney and Liver Transplant Recipients

“…Reported research has been focused on the effect of repeated boosting with monovalent mRNA- or viral vector–based vaccine doses. 31-34 Al Jurdi et al 35 found a significant increase in IgG levels against the RBD of BA.2.12.1 and BA.4/BA.5 subvariants (but not for B.1.1.529 or the ancestral strain) after a fourth monovalent vaccine dose among KT recipients. Additionally, both the neutralizing activity and the proportion of patients with neutralizing responses >30% against BA.4/BA.5 also increased with the booster.…”

“…29 In contrast, a number of studies have shown that a fourth dose of the bivalent vaccine induces higher neutralizing responses against BA.2- and BA.5-derived sublineages (including the BQ.1.1 and XBB.1 subvariants). 17,18 In a phase III trial, the BA.1-adapted BNT162b2 vaccine induced higher neutralizing activity than the original vaccine based on the ancestral strain, although cross-neutralization responses against BA.4/BA.5 subvariants did not substantially increase. 30 We are not aware of previous studies that have assessed the immunogenicity elicited by the BA.4/BA.5-adapted bivalent booster dose in the SOT setting.…”