Reduced antibody activity against SARS-CoV-2 B.1.617.2 Delta virus in serum of mRNA-vaccinated patients receiving Tumor Necrosis Factor-α inhibitors

SUMMARY Background Although vaccines effectively prevent COVID-19 in healthy individuals, they appear less immunogenic in individuals with chronic inflammatory diseases (CID) or receiving chronic immunosuppression therapy. Methods Here, we assessed a cohort of 77 CID patients treated as monotherapy with chronic immunosuppressive drugs for antibody responses in serum against historical and variant SARS-CoV-2 viruses after immunization with the BNT162b2 mRNA vaccine. Findings Longitudinal analysis showed the greatest reductions in neutralizing antibodies and Fc effector functions capacity in individuals treated with TNF-α inhibitors (TNFi), and this pattern appeared worse against B.1.617.2 Delta virus. Within five months of vaccination, serum neutralizing titers of all TNFi-treated patients tested fell below the presumed threshold correlate for antibody-mediated protection. However, TNFi-treated patients receiving a third mRNA vaccine dose boosted their serum neutralizing antibody titers by more than 16-fold. Conclusions Thus, vaccine boosting or administration of long-acting prophylaxis (e.g., monoclonal antibodies) likely will be required to prevent SARS-CoV-2 infection in this susceptible population. Funding. This study was supported by grants and contracts from NIH (R01 AI157155, R01AI151178, HHSN75N93019C00074, NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contracts HHSN272201400008C and 75N93021C00014, and the Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051).