Background: Kidney transplant recipients (KTR) have a diminished response to SARS-CoV-2 vaccination in comparison to immunocompetent individuals. Deeper understanding of the antibody response in KTRs following third-dose vaccination would enable identification of those who remain unprotected against Omicron and require additional treatment strategies. Methods: We profiled antibody responses in KTRs pre- and at one and three months post-third-dose SARS-CoV2 mRNA-based vaccine. Anti-spike and anti-RBD IgG levels were determined by ELISA. Neutralization against wild-type, Beta, Delta and Omicron (BA.1) variants was determined using a SARS-CoV-2 spike pseudotyped lentivirus assay. Results: 44 KTRs were analysed at 1 and 3 months (n=26) post-third-dose. At one month, the proportion of participants with a robust antibody response had increased significantly from baseline, but Omicron-specific neutralizing antibodies were detected in just 45% of KTRs. Median binding antibody levels declined at 3 months, but the proportion of KTRs with a robust antibody response was unchanged. 38.5% KTRs maintained Omicron-specific neutralization at 3 months. No clinical variables were significantly associated with detectable Omicron neutralizing antibodies, but anti-RBD titres appeared to identify those with Omicron-specific neutralizing capacity. Conclusion: Over 50% of KTRs lack an Omicron-specific neutralization response 1 month following a third mRNA-vaccine dose. Among responders, binding and neutralizing antibody responses were well preserved at 3 months. Anti-RBD antibody titres may be a useful identifier of patients with detectable Omicron neutralizing antibody response. Trial registration: Clinical Trials Ontario: ID 3604

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf. ACG has received research funds from a research contract with Providence Therapeutics Holdings, Inc for other projects not directly related to this manuscript. KY has received honoraria from Astra Zeneca. AL has received research funds/contracts from AstraZeneca; Certa; Otsuka; Reata; Retrophin; The George Institute; Chinook Therapeutics; Boeingher Ingelheim; CIHR; Janssen; Merck; Oxford Clinical Trials; Kidney Foundation of Canada; Merck; Amgen; Bayer; Johnson and Johnson; Retrophin; Reata; National Institute of Health; NIDDK. AL has received honoraria from GSK, Takeda; Reata; Astra Zeneca and Janssen. MJO has received honoraria from Baxter Healthcare, and serves on advisory boards for Janssen and Amgen. No other authors have conflicts of interest to disclose.

This work was funded by the COVID Immunity Task Force which is supported by the Government of Canada, and the St. Michael's Hospital Foundation.

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