Baltimore, MD—Concerns are being raised about how effectively immunocompromised patients can mount an immune response after the first of two doses of a SARS-CoV-2 messenger RNA (mRNA) vaccine.

A research letter published in JAMA suggests that, in those patients, the immune response to vaccination might be blunted.

To add to understanding of that phenomenon, Johns Hopkins University School of Medicine–led researchers recruited recipients across the United States through social media to participate in a prospective cohort. Included were 436 transplant recipients who underwent SARS-CoV-2 vaccination between December 16, 2020, and February 5, 2021. Participants underwent either at-home blood sampling with the TAPII blood collection device (Seventh Sense Biosystems) or standard venipuncture.

None of the participants, who had a median age of 55.9 years and a median time since transplant of 6.2 years, had a prior polymerase chain reaction–confirmed diagnosis of COVID-19. Most of the patients, 61%, were women, and 89% were white. Receipt of the Pfizer-BioNTech and Moderna vaccines were about half-and-half. Their maintenance immunosuppression regimens included tacrolimus (83%), corticosteroids (54%), mycophenolate (66%), azathioprine (9%), sirolimus (4%), and everolimus (2%).

Researchers tested the TAPII samples using an enzyme immunoassay (EUROIMMUN) that tests for antibodies to the S1 domain of the SARS-CoV-2 spike protein, while the venipuncture samples were tested using the anti–SARS-CoV-2 S enzyme immunoassay (Roche Elecsys) that tests for antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein.

“Both tests are semiquantitative, correspond to mRNA vaccine antigens, and are consistently correlated with neutralizing immunity,” according to the report. “The sensitivity and specificity of the enzyme immunoassays are excellent for detection of the antispike humoral response to SARS-CoV-2 infection (sensitivity of 87.1% and specificity of 98.9% for EUROIMMUN and sensitivity of 84.0% and specificity of 100% for Roche Elecsys) and are analogous to the antispike antibody assays used during immunogenicity assessments in mRNA vaccine clinical trials.”

Researchers report that, at a median of 20 days (IQR, 17-24 days) after the first dose of vaccine, antibody (anti-S1 or anti–receptor-binding domain) was detectable in 76 of 436 participants (17%; 95% CI, 14%-21%).

“Transplant recipients receiving anti–metabolite maintenance immunosuppression therapy were less likely to develop an antibody response than those not receiving such immunosuppression therapy (37% vs. 63%, respectively; adjusted incidence rate ratio [IRR], 0.22 [95% CI, 0.15-0.34], P < .001),” the authors explain. “Older transplant recipients were less likely to develop an antibody response (adjusted IRR, 0.83 [95% CI, 0.73-0.93] per 10 years, P = .002). Those who received mRNA-1273 were more likely to develop an antibody response than those receiving BNT162b2 (69% vs. 31%, respectively; adjusted IRR, 2.15 [95% CI, 1.29-3.57], P = .003). This association was similar in a sensitivity analysis limited to those tested 14 to 21 days after vaccination (n = 245; adjusted IRR, 2.29 [95% CI, 1.32-3.94], P = .003).”

The authors express concern about the ramifications of their results, noting, “These findings of poor antispike antibody responses in organ transplant recipients after the first dose of mRNA vaccines suggest that such patients may remain at higher early risk for COVID-19 despite vaccination. Deeper immunophenotyping of transplant recipients after vaccination, including characterization of memory B-cell and T-cell responses, will be important in determining vaccination strategies as well as immunologic responses after the second dose.”

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