*Purpose: Given substantial challenges with vaccine allocation and evidence for short-term vaccine efficacy after a single dose of SARS-CoV-2 mRNA vaccines in clinical trials, some have proposed prioritizing first dose administration to reduce COVID-19 morbidity, potentially resulting in delays of second dose administration, or even purposefully withholding second doses for much longer intervals than evaluated in the clinical trials. However, this evidence is largely based off of the early vaccine trials which largely excluded immunocompromised patients. To better understand the immunogenicity of the available SARS-CoV-2 vaccines in immunocompromised individuals, we quantified the humoral response to the first dose of SARS-CoV-2 vaccine in solid organ transplant recipients (SOTRs).

*Methods: SOTRs who underwent SARS-CoV-2 vaccination were recruited to participate in this study. Participants underwent at-home blood sampling with the TAPII^TM Blood Collection Device (7SBio, Medford, MA) or venipuncture. TapII^TM samples were tested on the EUROIMMUN enzyme immunoassay (EIA) which tests for IgG to SARS-CoV-2 spike protein. Venipuncture samples were tested on the Roche Elecsys® EIA which tests for antibodies against the receptor binding domain of the SARS-CoV-2 spike protein. Both tests are semi-quantitative and consistent correlates of neutralizing immunity.

*Results: We studied 279 SOTRs between 12/29/20-2/12/21. None had a prior COVID-19. Median (IQR) age was 51 (40-65) years, 64% were female, 87% were white, and 6% Hispanic/Latino. Median (IQR) time since transplant was 6 (3-13) years; maintenance immunosuppression included tacrolimus (96%), steroids (53%), mycophenolate (74%), azathioprine (9%), sirolimus (4%), everolimus (4%). At a median (IQR) of 20 (15-23) days after the first dose, antibody was detectable in only 16% of participants (binomial exact 95% confidence interval 12-21%). Those not on anti-metabolite maintenance immunosuppression were 5.2 times (95% CI 3.1-8.7, p <0.001) more likely to develop an antibody response.

*Conclusions: The vast majority of participants did not mount appreciable antibody responses. However, those not on anti-metabolite maintenance immunosuppression were more likely to develop antibody responses. These results contrast dramatically with the robust early immunogenicity observed in mRNA vaccine trials. These findings are an important reminder that any individual with potential immune compromise should not assume they have achieved an immune response to the SARS-CoV-2 vaccine after a first dose.

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