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

Autor: Lindsay Droit, Michael A. Paley, Rachel M. Presti, Florian Krammer, Jane A. O’Halloran, Rita E. Chen, Michael S. Diamond, Matthew J. Gorman, Dansu Yuan, Juan Manuel Carreño, Alfred H.J. Kim, Douglas A. Lauffenburger, Daniel Y. Zhu, Scott A. Handley, Gregory F. Wu, Wooseob Kim, Parakkal Deepak, Samantha Burdess, Salim Chahin, Galit Alter, Laura A. VanBlargan, Jackson S. Turner, Ali H. Ellebedy
Rok vydání: 2021
Předmět:
Zdroj: Med (New York, N.y.)
ISSN: 2666-6340
DOI: 10.1016/j.medj.2021.11.004
Popis: 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).
Graphical abstract
Context and significance In most individuals, mRNA vaccines effectively prevent severe disease following SARS-CoV-2 infection. However, the protective immunity induced by mRNA vaccines is diminished in immunocompromised individuals, and the effect of variant strains is unexplored. Here we evaluated serum antibody responses in individuals with chronic inflammatory disease after immunization with the Pfizer BNT162b2 mRNA vaccine. The lowest neutralizing antibody titers were observed in individuals treated with TNF-α inhibitors, and this pattern appeared to be worse against the delta virus, with the antibody levels falling below the presumed threshold correlate of protection. Administration of a third vaccine dose substantially boosted serum neutralizing titers. Our data suggest that vaccine boosting is needed to prevent SARS-CoV-2 infection in some immunocompromised populations, especially those receiving TNF-α inhibitor therapies.
Chen et al. assess serum antibodies from BNT162b2 mRNA-vaccinated individuals with chronic inflammatory disease receiving single immunosuppressive drug therapies. Individuals receiving TNF-α inhibitors (TNFi) had reduced antibody neutralizing and Fc effector function activity against the B.1.351 and B.1.617.2 variants. A third vaccine dose markedly boosted neutralizing titers in TNFi recipients.
Databáze: OpenAIRE
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