Aims To assess the short‐term immunogenicity to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) mRNA vaccine in a population of heart transplant (HTx) recipients. A prospective single‐centre cohort study of HTx recipients who received a two‐dose SARS‐CoV‐2 mRNA vaccine (BNT162b2, Pfizer‐BioNTech). Methods and results Whole blood for anti‐spike IgG (S‐IgG) antibodies was drawn at days 21–26 and at days 35–40 after the first vaccine dose. Geometric mean titres (GMT) ≥50 AU/mL were interpreted positive. Included were 42 HTx recipients at a median age of 61 [interquartile range (IQR) 44–69] years. Median time from HTx to the first vaccine dose was 9.1 (IQR 2.6–14) years. Only 15% of HTx recipients demonstrated the presence of positive S‐IgG antibody titres in response to the first vaccine dose [GMT 90 (IQR 54–229) AU/mL]. Overall, 49% of HTx recipients induced S‐IgG antibodies in response to either the first or the full two‐dose vaccine schedule [GMT 426 (IQR 106–884) AU/mL]. Older age [68 (IQR 59–70) years vs. 46 (IQR 34–63) years, P = 0.034] and anti‐metabolite‐based immunosuppression protocols (89% vs. 44%, P = 0.011) were associated with low immunogenicity. Importantly, 36% of HTx recipients who were non‐responders to the first vaccine dose became S‐IgG seropositive in response to the second vaccine dose. Approximately a half of HTx recipients did not generate S‐IgG antibodies following SARS‐CoV‐2 two‐dose vaccine. Conclusions The generally achieved protection from SARS‐CoV‐2 mRNA vaccination should be regarded with caution in the population of HTx recipients. The possible benefit of additive vaccine should be further studied.

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