The mRNA-1273 COVID-19 vaccine was more likely than the BNT162b2 vaccine to induce a strong humoral immunogenic response among patients with immunocompromised conditions, according to findings from a research letter published in JAMA Network Open.

In this cohort study, researchers enrolled patients with rheumatic and musculoskeletal diseases (RMDs) and those who were recipients of solid organ transplants (SOTs). All patients received 2 doses of a COVID-19 mRNA vaccine between December 2020 and July 2021. Between days 15 and 45 following receipt of the second vaccine dose, patients underwent semiquantitative testing to assess for antibodies against the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. The primary outcome measure was the number of patients who achieved anti-RBD titers of 250 U/mL or greater compared between patients who received the mRNA-1273 vaccine vs the BNT162b2 vaccine. A Poisson regression model was used to adjust for age, time since vaccination, and the number of current immunosuppressive medications. Repeat analysis was performed for patients with positive response thresholds of 50 and 100 U/mL.

The cohort comprised 1158 patients with RMDs and 697 recipients of SOTs, of whom 55.8% and 52.7% received the BNT162b2 vaccine, respectively. The remaining patients in both groups received the mRNA-1273 vaccine. Among patients in the RMD and SOT groups, the median age was approximately 47 and 62 years, and approximately 90% and 55% were women, respectively. The median number of immunosuppressants included in patients’ current medication regimens was similar among those in the RMD vs SOT groups (2 [IQR, 1-3] vs 2 [IQR, 2-3]).

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Among patients with RMDs who were not receiving immunosuppressive or immunomodulatory therapy, the number of patients in the BNT162b2 (n=118) and mRNA-1273 (n=102) groups who achieved the primary outcome (anti-RBD titers ≥250 U/mL) was similar (91.5% vs 93.1%, respectively; P =.69). Of patients with RMDs receiving immunosuppressive therapy, the rate of primary outcome achievement was increased among the mRNA-1273 (n=409) vs the BNT162b2 (n=529) vaccine recipients (79.2% vs 60.5%; P <.001).

Among patients in the SOT group who were not receiving immunosuppressive therapy, the rate of primary outcome was increased among the mRNA-1273 (n=128) vs the BNT162b2 (n=132) vaccine recipients (66.4% vs 44.7%; P <.001). Of patients in the SOT group who were receiving immunosuppressive therapy, recipients of the mRNA-1273 (n=202) vs BNT16b2 (n=235) vaccines also had an increased rate of primary outcome achievement (11.4% vs 4.3%; P =.01).

Similar results were observed for repeat analysis of anti-RBD titers of 50 and 100 U/mL between the patient groups. Of note, differential immunogenicity was most increased among patients in the SOT group who were receiving either mycophenolic acid or mycophenolate mofetil (incidence rate ratio, 2.62; 95% CI, 1.28-5.37; P =.01).

Study limitations included that patients’ self-reported their COVID-19 infection status, and the lack of testing for neutralizing antibodies.

“These findings suggest that choice of mRNA vaccine platform is important in optimizing immune responses to SARS-CoV-2 vaccination and can help inform strategies for booster doses in high-risk, immunosuppressed populations,” the researchers concluded.

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Mitchell J, Connolly CM, Chiang TP, et al. Comparison of SARS-CoV-2 antibody response after 2-dose mRNA-1273 vs BNT162b2 vaccines in incrementally immunosuppressed patients. JAMA Netw Open. 2022;5(5):e2211897. doi:10.1001/jamanetworkopen.2022.11897