Low antibody responses following 2 doses of the SARS-CoV-2 messenger RNA (mRNA) vaccine among transplant recipients suggest that this patient population remains susceptible to infection despite vaccination, according to researchers from Johns Hopkins University School of Medicine, whose findings were published in a research letter in JAMA.

Citing previous research reporting a low proportion (17%) of organ transplant patients mounting a positive antibody response to the first dose of SARS-CoV-2 mRNA vaccines, the Johns Hopkins team sought to evaluate antibody responses to a second vaccine dose in this patient population.

Solid organ transplant recipients (N=658) with no evidence of previous polymerase chain reaction (PCR)-confirmed COVID-19 infection were recruited across the United States for this prospective cohort study. Participants who had received both doses of SARS-CoV-2 mRNA vaccine before March 13, 2021, were followed through April 13, 2021, and assessed for their serologic response.


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At a median of 21 days after dose 1, antibodies were detected in 15% (95% CI, 12-18) of participants. At a median of 29 days after dose 2, antibodies were detected among 54% (95% CI, 50-58) of participants.

Among all participants, 15% had measurable antibody responses after both dose 1 and dose 2. An antibody response was detectable in 39% of participants after dose 2 but not dose 1, and 46% of participants had no response after dose 1 or dose 2.

Median antibody levels after dose 2 were 2.14 U/mL and 1.23 arbitrary units, as measured by Roche and EUROIMMUN assays, respectively. Among participants who had measurable antibody responses, the median antibody levels were 1.42.1 U/mL (Roche assay) and 6.48 arbitrary units (EUROIMMUN assay).

Stratified by antimetabolite maintenance immunosuppression, participants receiving vs not receiving antimetabolites had antibody responses after dose 1 and 2 (8% vs 32%), no response (57% vs 18%), or no antibody response after dose 1 but subsequent antibody after dose 2 (35% vs 50%), respectively.

The investigators noted that this study may have been limited by the fact that they did not assess patients for memory B-cell or T-cell responses or COVID-19 breakthrough infections. Lack of an immunocompetent control group and lack of assessment of postvaccination SARS-CoV-2 were also cited as limitations.

The study authors concluded that recipients of solid organ transplants likely are not sufficiently protected from COVID-19 by 2 doses of the SARS-CoV-2 mRNA vaccine. Further, transplant recipients undergoing immunosuppressive treatment with antimetabolite drugs are less likely to generate a clinically meaningful antibody response to this vaccine.

“Future studies,” the investigators emphasized, “should address interventions to improve vaccine responses in this population, including additional booster doses or immunosuppression modulation.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Boyarsky BJ, Werbel WA, Avery RK, et al. Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients. JAMA. Published online May 5, 2021. doi:10.1001/jama.2021.7489