Antibody Response to the Janssen/Johnson & Johnson SARS-CoV-2 Vaccine in Patients with Rheumatic and Musculoskeletal Diseases

In immunocompetent populations, the Janssen/Johnson & Johnson (J&J) SARS-CoV-2 vaccine induces antibody, CD4+ and CD8+ T-cell responses and offers protection against severe and symptomatic SARS-CoV-2 infection (1,2). This vaccine is an adenovirus serotype 26 (Ad26) vector expressing a stabilized SARS-CoV-2 spike (S) (Ad26.COV2. S), a platform without prior approval for use in the general population, or for patients with rheumatic and musculoskeletal diseases (RMD) (3). Patients on immunosuppressive therapy were excluded from the clinical trials (1,2) and early data has suggested that the J&J vaccine results in lower humoral immunity than mRNA vaccination in immunosuppressed transplant patients (4). Given the attenuated immunogenicity to mRNA-based SARS-CoV-2 vaccines in certain RMD patients (5), we studied the anti-spike antibody response to J&J SARS-CoV-2 vaccination in patients with RMD and compared them to recipients of the mRNA series.

We utilized our prospective cohort of RMD patients who underwent SARS-CoV-2 vaccination between 12/2020 to 5/2021 (5). We collected information on demographics, rheumatic diagnoses, and immunosuppressive medications. One month following completion of vaccine series (J&J or mRNA), serologic testing on the semi-quantitative Roche Elecsys^® anti-SARS-CoV-2 S enzyme immunoassay, which tests for antibodies against the receptor binding domain (RBD) of the SARS-CoV-2 spike protein was completed.

We compared the percentage of participants with detectable anti-RBD antibody in the J&J group (n=45) to the mRNA group (n=994) using Fisher's exact test (Supplemental Table 1). We compared the two vaccine platforms using logistic regression adjusting for age, sex, race, mycophenolate, rituximab, glucocorticoid and methotrexate use. We compared anti-RBD titers of the J&J group to those of the mRNA group using Wilcox rank-sum test. This study was approved by the Johns Hopkins Institutional Review Board (IRB00248540).

At a median (IQR) 29 days (28-32) after vaccination, anti-RBD antibody was detectable in 36 participants who received the J&J vaccine compared to 906 who completed the mRNA vaccine series (80% versus 92%, p=0.03). Those who received J&J vaccination had a higher odds of negative antibody response (OR 2.57, 95% CI 1.20-5.52, p=0.01) compared to those who completed the mRNA series. This association remained statistically significant in the adjusted logistic regression model (aOR 3.86, 95% CI 1.37-10.84 p=0.01). Consistent with prior findings, use of rituximab, mycophenolate and glucocorticoids had a statistically significant association with negative antibody response (Supplemental Table 2) (5). Median anti-RBD Ig titers in the J&J group were lower than the mRNA group (9.7 versus 250 U/mL; p<0.001) (Figure 1).

Figure 1.

SARS-CoV-2 Anti-Receptor Binding Domain Antibody Titers Among Recipients of mRNA versus J&J Vaccine. Titers could range from <0.4 to >250 U/mL. Positive antibody is defined as an anti-SARS-CoV-2 RBD antibody titer >0.79 U/mL.

In this observational study, we found that patients with RMD who received J&J vaccination had a lower rate of seroconversion compared to recipients of the mRNA series. One in five participants who received J&J vaccination did not mount a detectable antibody response. In those with a detectable antibody response, participants who received the J&J vaccine had lower antibody titers than the mRNA group. While no cutoff titer has been defined to associate with protection, there is a well-recognized role of neutralizing antibodies in protection against SARS-CoV-2 infection. A recent study estimated that an antibody neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20% of the mean convalescent level (6).

Limitations of this study include small sample size and non-randomized design. We did not analyze peri-vaccination immunosuppression dosing or timing.

These early results suggest that RMD patients who receive the J&J vaccine may have a more limited humoral response to J&J SARS-CoV-2 vaccination than recipients of the mRNA vaccine series. Optimization of J&J vaccine response in patients with RMD requires additional studies with larger sample size and evaluation of deeper immunophenotyping including memory B-cell and T-cell responses.

PATIENT AND PUBLIC INVOLVEMENT.

Patients were not involved in the design, conduct, or dissemination of the study, though this study was motivated by questions frequently posed by patients. The study has a public website (https://vaccineresponse.org/) and email account where we welcomed participants and the public to contact the research team. Results of the study will be shared with national RMD organizations for dissemination to their patient communities once published.