Reduced antibody activity against SARS-CoV-2 B.1.617.2 delta virus in serum of mRNA-vaccinated individuals receiving tumor necrosis factor-α inhibitors

Rita E. Chen, Matthew J. Gorman, Daniel Y. Zhu, Juan Manuel Carreño, Dansu Yuan, Laura A. VanBlargan, Samantha Burdess, Douglas A. Lauffenburger, Wooseob Kim, Jackson S. Turner, Lindsay Droit, Scott A. Handley, Salim Chahin, Parakkal Deepak, Jane A. O'Halloran, Michael A. Paley, Rachel M. Presti, Gregory F. Wu, Florian Krammer, Galit AlterAli H. Ellebedy, Alfred H.J. Kim, Michael S. Diamond

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Background: Although vaccines effectively prevent coronavirus disease 2019 (COVID-19) in healthy individuals, they appear to be less immunogenic in individuals with chronic inflammatory disease (CID) or receiving chronic immunosuppression therapy. Methods: Here we assessed a cohort of 77 individuals with CID treated as monotherapy with chronic immunosuppressive drugs for antibody responses in serum against historical and variant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses after immunization with the BNT162b2 mRNA vaccine. Findings: Longitudinal analysis showed the greatest reductions in neutralizing antibodies and Fc effector function capacity in individuals treated with tumor necrosis factor alpha (TNF-α) inhibitors (TNFi), and this pattern appeared to be worse against the B.1.617.2 delta virus. Within 5 months of vaccination, serum neutralizing titers of all TNFi-treated individuals tested fell below the presumed threshold correlate for antibody-mediated protection. However, TNFi-treated individuals receiving a third mRNA vaccine dose boosted their serum neutralizing antibody titers by more than 16-fold. Conclusions: Vaccine boosting or administration of long-acting prophylaxis (e.g., monoclonal antibodies) will likely be required to prevent SARS-CoV-2 infection in this susceptible population. Funding: This study was supported by grants and contracts from the NIH (R01 AI157155, R01AI151178, and HHSN75N93019C00074; NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contracts HHSN272201400008C and 75N93021C00014; and Collaborative Influenza Vaccine Innovation Centers [CIVIC] contract 75N93019C00051).

Original languageEnglish
Pages (from-to)1327-1341.e4
Issue number12
StatePublished - 10 Dec 2021


  • Fc effector functions
  • SARS-CoV-2
  • TNF inhibitors
  • Translation to patients
  • antibody
  • immunosuppression
  • mRNA vaccine
  • neutralization
  • variants of concern


Dive into the research topics of 'Reduced antibody activity against SARS-CoV-2 B.1.617.2 delta virus in serum of mRNA-vaccinated individuals receiving tumor necrosis factor-α inhibitors'. Together they form a unique fingerprint.

Cite this