Anti-TNFα Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases

on behalf of the Responses to COVID-19 Vaccine Israeli IBD Group

doi:10.3390/vaccines10081186

Anti-TNFα Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases

on behalf of the Responses to COVID-19 Vaccine Israeli IBD Group

Bar-Ilan University - Azrieli Faculty of Medicine

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNFα and 57 treated with anti-TNFα) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNFα had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNFα. Importantly, all seronegative subjects were patients with IBD; of those, >90% were treated with anti-TNFα. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients.

Original language	English
Article number	1186
Journal	Vaccines
Volume	10
Issue number	8
DOIs	https://doi.org/10.3390/vaccines10081186
State	Published - 26 Jul 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors.

Funding

We would like to thank the study participants for their effort and time. The Israeli IBD Society and Israeli GI association are thanked for their support, and Naim Abu-Freha for specific efforts to promote the study. The study was partially supported by a generous grant from The Leona M. and Harry B. Helmsley Charitable Trust. The Crohn’s and Colitis Foundation of Israel, the European Federation of Crohn’s and Colitis Associations and the AMICI group are thanked for partially funding the study and supporting recruitment efforts. This study was performed in collaboration with the Israeli Ministry of Health. NTF acknowledges the kind support of L. Cohen and the Milner Foundation. The study was partially supported by a generous grant from The Leona M. and Harry B. Helmsley Charitable Trust # G-2101-04950 (ID). The Crohn’s and Colitis Foundation of Israel and the European Federation of Crohn’s and Colitis Associations partially supported the study. N.TF and MGT were funded by Israel Science Foundation (ISF) Coronavirus grant #3711/20. NTF was funded by ISF grants #1422/18. MGT and MD were funded by the Bar-Ilan Dangoor Centre for Personalized Medicine. MGT was funded by an ISF grant #2475/19. M.D. was funded by an ISF grant #401/18. I.D.: consultation/advisory board: Abbvie, Athos, Arena, Cambridge Healthcare, Celltrion, Celgene/BMS, Ferring, Food Industries Organization, Iterative Scopes, Integra Holdings, Janssen, Neopharm, Pfizer, Rafa laboratories, Roche/Genentech, Sangamo, Sublimity, Takeda and Wildbio. Speaking/teaching: Abbvie, Altman, Celltrion, Celgene/BMS, Ferring, Falk Pharma, Janssen, MSD, Neopharm, Nestle, Pfizer, Rafa laboratories, Roche/Genentech, Sandoz and Takeda. ABGS: grant support from Takeda and Janssen, consultancy and lectures fees from Takeda, Janssen, Abbvie, Pfizer, Neopharm and BMS. EZ: has received research support and consulting fees from Janssen, Abbvie, Takeda, Neopharm, Celgene and Pfizer. All other authors declare they have no conflicts of interest.

Funders	Funder number
Crohn’s and Colitis Foundation of Israel
European Federation of Crohn’s and Colitis Associations
Bristol-Myers Squibb
Leona M. and Harry B. Helmsley Charitable Trust
Milner Foundation
Israel Science Foundation	2475/19, 1422/18, 401/18, 3711/20

Keywords

COVID-19
anti-SARS-CoV-2 antibodies
circulating B cells
cross-reactivity
mRNA-BNT162b2
serologic response longevity
vaccine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3390/vaccines10081186

Cite this

@article{e1c778fee9b84f84858893face87d663,

title = "Anti-TNFα Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases",

abstract = "Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNFα and 57 treated with anti-TNFα) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNFα had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNFα. Importantly, all seronegative subjects were patients with IBD; of those, >90% were treated with anti-TNFα. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients.",

keywords = "COVID-19, anti-SARS-CoV-2 antibodies, circulating B cells, cross-reactivity, mRNA-BNT162b2, serologic response longevity, vaccine",

author = "{on behalf of the Responses to COVID-19 Vaccine Israeli IBD Group} and Rabinowitz, {Keren Masha} and Michal Navon and Hadar Edelman-Klapper and Eran Zittan and {Bar-Gil Shitrit}, Ariella and Idan Goren and Irit Avni-Biron and Ollech, {Jacob E.} and Lev Lichtenstein and Hagar Banai-Eran and Henit Yanai and Yifat Snir and Pauker, {Maor H.} and Adi Friedenberg and Adva Levy-Barda and Arie Segal and Yelena Broitman and Eran Maoz and Baruch Ovadia and {Aharoni Golan}, Maya and Eyal Shachar and Shomron Ben-Horin and Nitsan Maharshak and Michal Mor and {Ben Zvi}, Haim and Rami Eliakim and Revital Barkan and Tali Sharar-Fischler and Sophy Goren and Noy Krugliak and Edward Pichinuk and Michael Mor and Michal Werbner and Joel Alter and Hanan Abu-Taha and Kawsar Kaboub and Moshe Dessau and Meital Gal-Tanamy and Dani Cohen and Freund, {Natalia T.} and Iris Dotan",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = jul,

day = "26",

doi = "10.3390/vaccines10081186",

language = "אנגלית",

volume = "10",

journal = "Vaccines",

issn = "2076-393X",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "8",

}

TY - JOUR

T1 - Anti-TNFα Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases

AU - on behalf of the Responses to COVID-19 Vaccine Israeli IBD Group

AU - Rabinowitz, Keren Masha

AU - Navon, Michal

AU - Edelman-Klapper, Hadar

AU - Zittan, Eran

AU - Bar-Gil Shitrit, Ariella

AU - Goren, Idan

AU - Avni-Biron, Irit

AU - Ollech, Jacob E.

AU - Lichtenstein, Lev

AU - Banai-Eran, Hagar

AU - Yanai, Henit

AU - Snir, Yifat

AU - Pauker, Maor H.

AU - Friedenberg, Adi

AU - Levy-Barda, Adva

AU - Segal, Arie

AU - Broitman, Yelena

AU - Maoz, Eran

AU - Ovadia, Baruch

AU - Aharoni Golan, Maya

AU - Shachar, Eyal

AU - Ben-Horin, Shomron

AU - Maharshak, Nitsan

AU - Mor, Michal

AU - Ben Zvi, Haim

AU - Eliakim, Rami

AU - Barkan, Revital

AU - Sharar-Fischler, Tali

AU - Goren, Sophy

AU - Krugliak, Noy

AU - Pichinuk, Edward

AU - Mor, Michael

AU - Werbner, Michal

AU - Alter, Joel

AU - Abu-Taha, Hanan

AU - Kaboub, Kawsar

AU - Dessau, Moshe

AU - Gal-Tanamy, Meital

AU - Cohen, Dani

AU - Freund, Natalia T.

AU - Dotan, Iris

PY - 2022/7/26

Y1 - 2022/7/26

N2 - Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNFα and 57 treated with anti-TNFα) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNFα had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNFα. Importantly, all seronegative subjects were patients with IBD; of those, >90% were treated with anti-TNFα. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients.

AB - Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNFα and 57 treated with anti-TNFα) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNFα had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNFα. Importantly, all seronegative subjects were patients with IBD; of those, >90% were treated with anti-TNFα. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients.

KW - COVID-19

KW - anti-SARS-CoV-2 antibodies

KW - circulating B cells

KW - cross-reactivity

KW - mRNA-BNT162b2

KW - serologic response longevity

KW - vaccine

UR - http://www.scopus.com/inward/record.url?scp=85138101178&partnerID=8YFLogxK

U2 - 10.3390/vaccines10081186

DO - 10.3390/vaccines10081186

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 35893835

AN - SCOPUS:85138101178

SN - 2076-393X

VL - 10

JO - Vaccines

JF - Vaccines

IS - 8

M1 - 1186

ER -

Anti-TNFα Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this