Abstract
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 language | English |
|---|---|
| Pages (from-to) | 1327-1341.e4 |
| Journal | Med |
| Volume | 2 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 10 2021 |
Keywords
- Fc effector functions
- SARS-CoV-2
- TNF inhibitors
- Translation to patients
- antibody
- immunosuppression
- mRNA vaccine
- neutralization
- variants of concern
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In: Med, Vol. 2, No. 12, 10.12.2021, p. 1327-1341.e4.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - 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
AU - Chen, Rita E.
AU - Gorman, Matthew J.
AU - Zhu, Daniel Y.
AU - Carreño, Juan Manuel
AU - Yuan, Dansu
AU - VanBlargan, Laura A.
AU - Burdess, Samantha
AU - Lauffenburger, Douglas A.
AU - Kim, Wooseob
AU - Turner, Jackson S.
AU - Droit, Lindsay
AU - Handley, Scott A.
AU - Chahin, Salim
AU - Deepak, Parakkal
AU - O'Halloran, Jane A.
AU - Paley, Michael A.
AU - Presti, Rachel M.
AU - Wu, Gregory F.
AU - Krammer, Florian
AU - Alter, Galit
AU - Ellebedy, Ali H.
AU - Kim, Alfred H.J.
AU - Diamond, Michael S.
N1 - Funding Information: 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). The Alter laboratory was supported by the Ragon Institute, the Massachusetts Consortium on Pathogen Readiness (MassCPR), the NIH (3R37AI080289-11S1, R01AI146785, U19AI42790, U19AI135995, U19AI42790, 1U01CA260476, and CIVIC75N93019C00052), Gates Foundation Global Health Vaccine Accelerator Platform funding (OPP1146996 and INV-001650), and the Musk Foundation. M.P. was supported by the Scientist Development Award from the Rheumatology Research Foundation. P.D. is supported by a Junior Faculty Development Award from the American College of Gastroenterology and IBD Plexus of the Crohn's & Colitis Foundation. A.H.J.K. is supported by the Rheumatology Research Foundation, NIH/NIAMS P30 AR073752, and PCORI SDM2017C28224. G.F.W. was supported by grant funding from the NIH (R01 NS106289) and the NMSS (RG-1802-30253). The COVaRiPAD study was supported by The Leona M. and Harry B. Helmsley Charitable Trust, the Washington University Digestive Disease Research Core Center (NIDDK P30DK052574), the Washington University Rheumatic Diseases Research Resource-Based Center (NIAMS P30AR073752), the Judy Miniace Research Fund for the Washington University Lupus Clinic, Siteman Cancer Center grant P30CA091842 from the NIH/NCI, and the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the NIH/NCATS. We thank Richard Webby and Pei-Yong Shi for some of the viruses used in this study and Kimberly E. Taylor at University of California, San Francisco for statistical support. R.E.C. and L.A.V. performed and analyzed neutralization assays. M.J.G. D.Y. and D.Y.Z. performed and analyzed effector function analyses. J.M.C. performed and analyzed ELISA data. L.D. and S.A.H. performed and analyzed next-generation sequencing of viral stocks. P.D. M.P. R.M.P. J.A.O. S.C. G.F.W. A.H.E. and A.H.J.K. designed the clinical studies and provided human samples. S.B. W.K. and J.S.T. processed clinical samples. R.E.C. A.H.J.K. and M.S.D. performed and oversaw the statistical analysis. R.E.C. and M.S.D. had unrestricted access to all of the data in the paper. P.D. D.A.L. F.K. G.A. A.H.E. A.H.J.K. and M.S.D. obtained funding. G.A. and M.S.D. supervised the research. R.E.C. and M.S.D. wrote the initial draft, with the other authors providing editorial comments. All authors agreed to submit the manuscript, read and approved the final draft, and take full responsibility for its content, including the accuracy of the data. M.S.D. is a consultant for Inbios, Vir Biotechnology, Senda Biosciences, and Carnival Corporation and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Vir Biotechnology, Moderna, and Emergent BioSolutions. F.K. is a coinventor on a patent application for serological assays and SARS-CoV-2 vaccines (international application numbers PCT/US2021/31110 and 62/994,252). A.H.J.K. participated in consulting, advisory board, or speaker's bureau for Alexion Pharmaceuticals; Aurinia Pharmaceuticals; Exagen Diagnostics, Inc.; and GlaxoSmithKline and received unrelated funding support under a sponsored research agreement from GlaxoSmithKline. The Ellebedy laboratory received funding under sponsored research agreements that are unrelated to current study from Emergent BioSolutions and AbbVie. A.H.E. is a consultant for Mubadala Investment Company and the founder of ImmuneBio Consulting LLC. A.H.E. M.S.D. and J.S.T. are recipients of a licensing agreement with Abbvie Inc. for commercial development of a SARS-CoV-2 mAb not described in this study. J.S.T. is a consultant for Gerson Lehrman Group. S.C. received research funding from Biogen and received speaking and/or consulting fees from Biogen, Novartis, Sanofi Genzyme, Genentech, and Bristol Myers Squibb. P.D. has participated in consulting, advisory board, or speaker's bureau for Janssen, Pfizer, Prometheus Biosciences, Boehringer Ingelheim, AbbVie, and Arena Pharmaceuticals and received funding under an unrelated sponsored research agreement from Takeda Pharmaceutical, Arena Pharmaceuticals, Bristol Myers Squibb-Celgene, and Boehringer Ingelheim. G.F.W. has received honoraria for consulting from Novartis and Genentech, Inc. and research funding from Biogen, EMD Serono, and Roche. F.K. has consulted for Merck, Curevac, and Pfizer in the past and is currently consulting for Pfizer, Seqirus, and Avimex. The Krammer laboratory is collaborating with Pfizer on animal models of SARS-CoV-2. G.A. is the founder of SeromYx Systems Inc. and an equity holder of Leyden Labs. Funding Information: 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 ). The Alter laboratory was supported by the Ragon Institute , the Massachusetts Consortium on Pathogen Readiness (MassCPR), the NIH ( 3R37AI080289-11S1 , R01AI146785 , U19AI42790 , U19AI135995 , U19AI42790 , 1U01CA260476 , and CIVIC75N93019C00052 ), Gates Foundation Global Health Vaccine Accelerator Platform funding ( OPP1146996 and INV-001650 ), and the Musk Foundation . M.P. was supported by the Scientist Development Award from the Rheumatology Research Foundation . P.D. is supported by a Junior Faculty Development Award from the American College of Gastroenterology and IBD Plexus of the Crohn's & Colitis Foundation . A.H.J.K. is supported by the Rheumatology Research Foundation , NIH/NIAMS P30 AR073752 , and PCORI SDM2017C28224 . G.F.W. was supported by grant funding from the NIH ( R01 NS106289 ) and the NMSS ( RG-1802-30253 ). The COVaRiPAD study was supported by The Leona M. and Harry B. Helmsley Charitable Trust , the Washington University Digestive Disease Research Core Center ( NIDDK P30DK052574 ), the Washington University Rheumatic Diseases Research Resource-Based Center ( NIAMS P30AR073752 ), the Judy Miniace Research Fund for the Washington University Lupus Clinic , Siteman Cancer Center grant P30CA091842 from the NIH/NCI , and the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the NIH/NCATS . We thank Richard Webby and Pei-Yong Shi for some of the viruses used in this study and Kimberly E. Taylor at University of California, San Francisco for statistical support. Publisher Copyright: © 2021 Elsevier Inc.
PY - 2021/12/10
Y1 - 2021/12/10
N2 - 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).
AB - 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).
KW - Fc effector functions
KW - SARS-CoV-2
KW - TNF inhibitors
KW - Translation to patients
KW - antibody
KW - immunosuppression
KW - mRNA vaccine
KW - neutralization
KW - variants of concern
UR - http://www.scopus.com/inward/record.url?scp=85120737082&partnerID=8YFLogxK
U2 - 10.1016/j.medj.2021.11.004
DO - 10.1016/j.medj.2021.11.004
M3 - Article
C2 - 34812429
AN - SCOPUS:85120737082
SN - 2666-6359
VL - 2
SP - 1327-1341.e4
JO - Med
JF - Med
IS - 12
ER -