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 Alter; Ali H. Ellebedy; Alfred H.J. Kim; Michael S. Diamond

doi:10.1016/j.medj.2021.11.004

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 journal › Article › peer-review

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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	https://doi.org/10.1016/j.medj.2021.11.004
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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Chen, R. E., Gorman, M. J., Zhu, D. Y., Carreño, J. M., Yuan, D., VanBlargan, L. A., Burdess, S., Lauffenburger, D. A., Kim, W., Turner, J. S., Droit, L., Handley, S. A., Chahin, S., Deepak, P., O'Halloran, J. A., Paley, M. A., Presti, R. M., Wu, G. F., Krammer, F., ... Diamond, M. S. (2021). 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. Med, 2(12), 1327-1341.e4. https://doi.org/10.1016/j.medj.2021.11.004

@article{05b204d5e38949b9b5db1236208c6488,

title = "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",

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).",

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

author = "Chen, {Rita E.} and Gorman, {Matthew J.} and Zhu, {Daniel Y.} and Carre{\~n}o, {Juan Manuel} and Dansu Yuan and VanBlargan, {Laura A.} and Samantha Burdess and Lauffenburger, {Douglas A.} and Wooseob Kim and Turner, {Jackson S.} and Lindsay Droit and Handley, {Scott A.} and Salim Chahin and Parakkal Deepak and O'Halloran, {Jane A.} and Paley, {Michael A.} and Presti, {Rachel M.} and Wu, {Gregory F.} and Florian Krammer and Galit Alter and Ellebedy, {Ali H.} and Kim, {Alfred H.J.} and Diamond, {Michael S.}",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = dec,

day = "10",

doi = "10.1016/j.medj.2021.11.004",

language = "English",

volume = "2",

pages = "1327--1341.e4",

journal = "Med",

issn = "2666-6359",

number = "12",

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Chen, RE, Gorman, MJ, Zhu, DY, Carreño, JM, Yuan, D, VanBlargan, LA, Burdess, S, Lauffenburger, DA, Kim, W, Turner, JS, Droit, L, Handley, SA , Chahin, S , Deepak, P, O'Halloran, JA, Paley, MA , Presti, RM, Wu, GF, Krammer, F, Alter, G, Ellebedy, AH, Kim, AHJ & Diamond, MS 2021, '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', Med, vol. 2, no. 12, pp. 1327-1341.e4. https://doi.org/10.1016/j.medj.2021.11.004

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.

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 -

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

Abstract

Keywords

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