Methotrexate Hampers Immunogenicity to BNT162b2 mRNA COVID-19 Vaccine in Immune-Mediated Inflammatory Disease

Abstract

Objective: To investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment. Methods: Established patients at NYU Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunization. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analyzed for humoral response. Cellular immune response to SARS-CoV-2 was further analyzed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany were also analyzed for humoral immune response. Results: Although healthy subjects (n=208) and IMID patients on biologic treatments (mostly on TNF blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, IMID patients do not demonstrate an increase in CD8+ T cell activation after vaccination. Conclusions: In two independent cohorts of IMID patients, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunization efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.

Robust immune responses after one dose of BNT162b2 mRNA vaccine dose in SARS-CoV-2 experienced individuals

“…Consistent with this, our Spike antibody avidity experiments demonstrate progressive maturation of serum antibodies following mRNA vaccination, with increasing avidity through at least a month post second vaccination. However, much remains to be learned about Tfh responses in this context and whether these cells play a role in poor antibody responses after mRNA vaccination (61) . Two prior studies evaluated mRNA vaccination for influenza in humans and non-human primates and found robust induction of ICOS + CXCR3 + PD-1 + cTfh responses and neutralizing antibodies (48, 62) .…”

Altered cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy

“…Whereas SARS-CoV-2 mRNA-based vaccination has been successful in generating robust B cell and T cell mediated vaccine responses in healthy individuals 44,45,47,48,50,51 , less is known about responses to these vaccines in patients with autoimmune conditions, particularly those receiving immunosuppressive or immune cell-depleting agents 29,52 . To examine the impact of anti-CD20 (aCD20) monoclonal antibody therapy on responses to SARS-CoV-2 mRNA vaccination, we recruited 20 patients with multiple sclerosis (MS) treated with aCD20 (MS-aCD20) and compared their vaccine-induced immune responses to 10 healthy control (HC) subjects within the University of Pennsylvania Health System (Extended Data Table 1).…”

SARS-CoV-2 infection after vaccination in patients with inflammatory rheumatic and musculoskeletal diseases

“…1 2 Some common rheumatic and musculoskeletal disease (RMD) medications have been highlighted as possible influential factors on immunogenicity, particularly rituximab (RTX), mycophenolate mofetil (MMF), methotrexate (MTX), abatacept and glucocorticoids. [3][4][5][6][7] The European Alliance of Associations for Rheumatology (EULAR) launched a COVID-19 registry in March 2020, capturing COVID-19 outcomes in the European RMD population. Questions on reinfection and vaccination were added in January 2021.…”