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

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

doi:10.3390/vaccines10081186

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

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

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

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Abstract

Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNF alpha) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNF alpha (non-anti-TNF alpha) 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-TNF alpha and 57 treated with anti-TNF alpha) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNF alpha had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNF alpha. Importantly, all seronegative subjects were patients with IBD; of those, >90TNF alpha. 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 - 1 Aug 2022
Externally published	Yes

Keywords

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

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10.3390/vaccines10081186

Cite this

Rabinowitz, K. M., Navon, M., Edelman-Klapper, H., Zittan, E., Bar-Gil Shitrit, A., Goren, I., Avni-Biron, I., Ollech, J. E., Lichtenstein, L., Banai-Eran, H., Yanai, H., Snir, Y., Pauker, M. H., Friedenberg, A., Levy-Barda, A., Segal, A., Broitman, Y., Maoz, E., Ovadia, B., ... Israeli, R. COVID. V. (2022). Anti-TNF alpha Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases. Vaccines, 10(8), Article 1186. https://doi.org/10.3390/vaccines10081186

@article{73f65c51a42c46a5879e44f44e1ccb2a,

title = "Anti-TNF alpha 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 (TNF alpha) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNF alpha (non-anti-TNF alpha) 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-TNF alpha and 57 treated with anti-TNF alpha) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNF alpha had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNF alpha. Importantly, all seronegative subjects were patients with IBD; of those, >90TNF alpha. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients.",

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

author = "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 and Israeli, {Responses COVID-19 Vaccine}",

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

year = "2022",

month = aug,

day = "1",

doi = "10.3390/vaccines10081186",

language = "אנגלית",

volume = "10",

journal = "Vaccines",

issn = "2076-393X",

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

number = "8",

}

Rabinowitz, KM, Navon, M, Edelman-Klapper, H, Zittan, E, Bar-Gil Shitrit, A, Goren, I, Avni-Biron, I, Ollech, JE, Lichtenstein, L, Banai-Eran, H, Yanai, H, Snir, Y, Pauker, MH, Friedenberg, A, Levy-Barda, A, Segal, A, Broitman, Y, Maoz, E, Ovadia, B, Aharoni Golan, M, Shachar, E, Ben-Horin, S, Maharshak, N, Mor, M, Ben Zvi, H, Eliakim, R, Barkan, R, Sharar-Fischler, T, Goren, S, Krugliak, N, Pichinuk, E, Mor, M, Werbner, M, Alter, J, Abu-Taha, H, Kaboub, K, Dessau, M, Gal-Tanamy, M, Cohen, D, Freund, NT, Dotan, I & Israeli, RCOVIDV 2022, 'Anti-TNF alpha Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases', Vaccines, vol. 10, no. 8, 1186. https://doi.org/10.3390/vaccines10081186

TY - JOUR

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

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

AU - Israeli, Responses COVID-19 Vaccine

PY - 2022/8/1

Y1 - 2022/8/1

N2 - Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNF alpha) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNF alpha (non-anti-TNF alpha) 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-TNF alpha and 57 treated with anti-TNF alpha) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNF alpha had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNF alpha. Importantly, all seronegative subjects were patients with IBD; of those, >90TNF alpha. 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 (TNF alpha) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNF alpha (non-anti-TNF alpha) 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-TNF alpha and 57 treated with anti-TNF alpha) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNF alpha had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNF alpha. Importantly, all seronegative subjects were patients with IBD; of those, >90TNF alpha. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients.

KW - COVID-19

KW - vaccine

KW - mRNA-BNT162b2

KW - anti-SARS-CoV-2 antibodies

KW - serologic response longevity

KW - circulating B cells

KW - cross-reactivity

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???

SN - 2076-393X

VL - 10

JO - Vaccines

JF - Vaccines

IS - 8

M1 - 1186

ER -

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

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Keywords

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