3rd and 4th Doses of Mrna Vaccines Broaden and Prolong Immune Responses to sars-cov-2 in Immunocompromised Patients with Immune-mediated Inflammatory Diseases

Abstract Text: The IMPACT (immune response after COVID-19 vaccination during maintenance therapy in immune-mediated inflammatory diseases) observational study investigated the immunogenicity of SARS-CoV-2 mRNA vaccines in 161 patients with immune-mediated inflammatory diseases (IMID: inflammatory bowel disease, rheumatic or psoriatic disease), with or without maintenance immunosuppressive therapies, compared to healthy controls (HC). IMID patients were untreated or treated with anti-IL-17, anti-IL-12/23, anti-IL-23, methotrexate/azathioprine (MTX/AZA), anti-TNF, or anti-TNF+MTX/AZA. Antibody and T cell responses and neutralization of wildtype (WT) and variants of concern (VOC) were assessed pre and post successive vaccine doses. Compared to HC, IMID patients exhibited accelerated waning of antibody and T cell responses after dose 2. A 3rd vaccine dose restored these responses, and there was reduced decay after 3rd and 4th doses. While IFNy responses maximized after 1 dose in all participants, IMID patients required a 3rd vaccine dose to maintain stability of IFNy responses. Maximal IL-2 responses required 3 doses and IL-4 production continued to increase after 4 doses. Neutralization of VOC was lower in IMID patients, while all patients exhibited robust T cell immunity to VOC. Anti-TNF treated patients had the lowest antibody and neutralization responses, even after 4 doses. The 4th dose subtly affected the magnitude of immune responses in all patients and stabilized the neutralization response against VOC in IMID patients. Our study demonstrates that IMID patients show greater waning of immunity to SARS-CoV-2 than HC, stressing the importance of 3rd and 4th doses of mRNA vaccines in the immunocompromised to stabilize and broaden responses to SARS-CoV-2.