Methotrexate Impairs Immunogenicity of BNT162b2 SARS-CoV-2 Vaccine

Studies have shown over 90% immunogenicity and efficacy rates for mRNA vaccines in the immunocompetent population globally. However, the response of patients who have immune-mediated inflammatory diseases (IMIDs) and are on immunomodulatory medications is not clear. Researchers from Germany and the USA recently investigated the cellular and humoral immune responses of patients with IMIDs on immunomodulatory treatment to mRNA COVID-19 vaccines. As part of the study, 51 patients with IMID at NYU Langone Health receiving the BNT162b2 mRNA vaccine were evaluated at baseline and after the second dose of the vaccine. About 26 healthy individuals acted as controls.


The researchers analyzed Immunoglobulin G (IgG) antibody responses to the SARS-CoV-2 spike protein. Cellular immune response to the virus was further analyzed using high-parameter spectral flow cytometry. A second independent cohort of 31 patients with IMID and 182 controls from Erlangen, Germany, were also assessed for humoral immune responses. The results showed that individuals with IMID on methotrexate showed up to a 62% reduced rate of immunogenicity to the BNT162b2 vaccination. Those who were on anti-cytokine or non-methotrexate oral medications showed similar immunogenicity levels compared to healthy controls who had over an immunogenicity rate of over 90%.


Similarly, the BNT162b2 vaccination did not induce an activated CD8+ T cell response in patients with IMID on methotrexate. This study looked at the humoral and cellular immune responses to 2 doses of the BNT162b2 mRNA vaccine for COVID-19 in patients with IMID on immunomodulators and compared them with healthy controls. The findings showed that in 2 geographically independent cohorts of IMID patients, methotrexate – a widely used immunomodulator in the treatment of IMIDs – adversely impacted humoral as well as cellular immune responses of the patients to COVID-19 mRNA vaccines.


Ref Link: https://www.medrxiv.org/content/10.1101/2021.05.11.21256917v1

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