*Purpose: To determine the incidence of de novo donor-specific antibodies (DSAs) in recipients of orthotopic heart transplants (OHT) who received an mRNA vaccine against SARS-CoV-2.

*Methods: This was a case series that followed 112 OHT recipients (mean age 61.5 years [SD 14.5]; 77 men (68.75%)) from Dec 2020 to Nov 2021 at Emory University Hospital in Atlanta, GA (single site) after receiving at least 2 doses of SARS-CoV-2 mRNA vaccinations (Moderna or Pfizer). The median time between transplantation and initial vaccination was 9.6 years (IQR 4.27 to 18.2). HLA antibodies were assayed by blood test to monitor for de novo development of DSAs. Statistical analyses were performed using SPSS, Inc v27.0.

*Results: During a median follow-up time of 100 days (range 20-225), de novo DSAs were detected in 8 patients (7.08%) with a median time to detection of 75 days (12-138). Of those that developed de novo DSAs, 7 (87.5%) were HLA class II. 20 (18%) patients had pre-formed DSAs prior to vaccination and these remained unchanged during the follow-up period.

*Conclusions: Based on this limited series, we report that the SARS-CoV-2 mRNA vaccine may not be a significant source of allosensitization. The rate of de novo DSA development in our post-vaccination population was not elevated when compared to previously estimated rates among OHT recipients (25-35%). Based on these findings, we recommend transplant centers continue to encourage vaccination among heart transplant candidates. Limitations to this study include not having a parallel population of unvaccinated patients to directly compare DSA incidence/prevalence. Further monitoring of DSA development after a third booster SARS-CoV-2 mRNA vaccine may be necessary.

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