Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab

Simeng Lin; Nicholas A Kennedy; Aamir Saifuddin; Diana Muñoz Sandoval; Catherine J Reynolds; Rocio Castro Seoane; Sherine H Kottoor; Franziska P Pieper; Kai-Min Lin; David K Butler; Neil Chanchlani; Rachel Nice; Desmond Chee; Claire Bewshea; Malik Janjua; Timothy J McDonald; Shaji Sebastian; James L Alexander; Laura Constable; James C Lee; Charles D Murray; Ailsa L Hart; Peter M Irving; Gareth-Rhys Jones; Klaartje B Kok; Christopher A Lamb; Charlie W Lees; Daniel M Altmann; Rosemary J Boyton; James R Goodhand; Nick Powell; Tariq Ahmad; CLARITY IBD study

doi:10.1038/s41467-022-28517-z

Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab

Nat Commun. 2022 Mar 16;13(1):1379. doi: 10.1038/s41467-022-28517-z.

Authors

Simeng Lin^#^{1

2}, Nicholas A Kennedy^#^{1

2}, Aamir Saifuddin^#^{3

4}, Diana Muñoz Sandoval^#⁵, Catherine J Reynolds⁵, Rocio Castro Seoane⁶, Sherine H Kottoor⁴, Franziska P Pieper⁵, Kai-Min Lin⁵, David K Butler⁵, Neil Chanchlani^{1

2}, Rachel Nice^{2

7}, Desmond Chee^{1

2}, Claire Bewshea², Malik Janjua^{1

2}, Timothy J McDonald⁷, Shaji Sebastian^{8

9}, James L Alexander^{4

10}, Laura Constable⁴, James C Lee^{11

12

13}, Charles D Murray¹¹, Ailsa L Hart³, Peter M Irving^{14

15}, Gareth-Rhys Jones^{16

17}, Klaartje B Kok^{18

19}, Christopher A Lamb^{20

21}, Charlie W Lees^{16

22}, Daniel M Altmann⁶, Rosemary J Boyton^#^{5

23}, James R Goodhand^#^{1

2}, Nick Powell^#^{4

10}, Tariq Ahmad^#^{24

25}; CLARITY IBD study

Collaborators

CLARITY IBD study:
Klaartje B Kok, Farjhana Bokth, Bessie Cipriano, Caroline Francia, Nosheen Khalid, Hafiza Khatun, Ashley Kingston, Irish Lee, Anouk Lehmann, Kinnari Naik, Elise Pabriaga, Nicolene Plaatjies, Kevin Samuels, Rebecca Saich, Hayley Cousins, Wendy Fraser, Rachel Thomas, Matthew Brown, Benjamin White, Nikolaos Kirkineziadis, Bernadette Tilley, Rafeeq Muhammed, Rehana Bi, Catherine Cotter, Jayne Grove, Kate Hong, Ruth Howman, Monica Mitchell, Sophie Clayton, Sugrah Sultan, Melanie Rooney, Charlotte Cottrill, Salil Singh, Chris Dawe, Robert Hull, Natalie Silva, Jonathan Manning, Lauren Finlayson, Allison Roebuck, Joy Dawson, Sunil Sonwalkar, Naomi Chambers, Matthew Robinson, Andrew Haigh, Lear Matapure, Tim Raine, Varun George, Christina Kapizioni, Konstantina Strongili, Tina Thompson, Mohamed Ahmed, Christos Kontos, Christophe Bourges, Isabella Barbutti, Megan E Gozzard, Philip Hendy, Rhian Bull, Patricia Costa, Lisa Davey, Hayley Hannington, Kribashnie Nundlall, Catarina Martins, Laura Avanzi, Jaime Carungcong, Sabrina Barr, Richard Appleby, Emma Johnson, Kath Phillis, Rachel Gascoyne, Amanda Crowder, Amanda Whileman, Ian London, Jenny Grounds, Emmeline Martin, Susie Pajak, Jude Price, Kathryn Cawley, Anjan Dhar, Ellen Brown, Amanda Cowton, Kimberley Stamp, Ben Warner, Carmel Stuart, Louise Lacey, Shanika de Silva, Clare Allcock, Philip Harvey, Lesley Jones, Elise Cooke, Johanne Brooks, Pearl Baker, Hannah Beadle, Carina Cruz, Debbie Potter, Joe Collum, Farzana Masters, Aashish Kumar, Samantha Coetzee, Mihaela Peiu, Becky Icke, Meena Raj, Edward Gaynor, Sibongile Chadokufa, Bonita Huggett, Hamza Meghari, Sara El-Khouly, Fevronia Kiparissi, Waffa Girshab, Andrew Claridge, Emily Fowler, Laura McCafferty, Karolina Christodoulides, Angela Clifford, Patrick Dawson, Sailish Honap, Samuel Lim, Raphael Luber, Karina Mahiouz, Susanna Meade, Parizade Raymode, Rebecca Reynolds, Anna Stanton, Sherill Tripoli, Naomi Hare, Senthuran Balachandran, Emma North, Jessica North, Bria Browne, Ella Jameson, Yih Harn Siaw, Lane Manzano, Jonathan Segal, Ibrahim Al-Bakir, Imran Khakoo, Nora Thoua, Katherine Davidson, Jagrul Miah, Lisa Canclini, Alex Hall, Melony Hayes, Sally Myers, Alison Talbot, Jack Turnbull, Emma Whitehead, Katie Stamp, Alison Pattinson, Verghese Mathew, Leanne Sherris, Angela Harvey, Lucy Hicks, Tara-Marie Byrne, Leilani Cabreros, Hannah Downing-Wood, Sophie Hunter, Hemanth Prabhudev, Sharmili Balarajah, Hajir Ibraheim, Melissa Torkizadeh, Jonathan W Lo, Zhigang Liu, Helen Sutherland, Elva Wilhelmsen, Katherine Mackintosh, Ajay M Verma, Juliemol Sebastian, Mohammad Farhad Peerally, Parizade Raymode, Anne-Marie Guerdette, Alexandra Kent, Lee Meng Choong, Benedetta Pantaloni, Pantelis Ravdas, Babu Vadamalayan, Stephen Foley, Becky Arnold, Cheryl Heeley, Wayne Lovegrove, Donna Sowton, Lynne Allsop, Heidi Gregory, Philip J Smith, Giovanna Bretland, Sarah King, Martina Lofthouse, Lindsey Rigby, Sreedhar Subramanian, David Tyrer, Kate Martin, Christopher Probert, Nikolaos Kamperidis, Temi Adedoyin, Manisha Baden, Jeannette Brown, Feba Chacko, Michela Cicchetti, Mohammad Aamir Saifuddin, Priya Yesupatham, Rohit Gowda, Maureen Williams, Karen Kemp, Rima Akhand, Glaxy Gray, Anu John, Maya John, Tasnim Mohammed, Diamond Sathe, Natasha Jones, Jennifer Soren, Michael Sprakes, Julie Burton, Patricia Kane, Stephanie Lupton, Jacqueline Bartholomew, George MacFaul, Diane Scaletta, Loria Siamia, Felicity Williams, Chloe Green, Zeljka Ver, Christopher A Lamb, Mary Doona, Ashleigh Hogg, Lesley Jeffrey, Andrew King, R Alexander Speight, Jennifer Doyle, Ruth Owen, Craig Mowat, Debbie Rice, Susan MacFarlane, Anne MacLeod, Samera Mohammed, Shona Murray, Anne Elliott, Mary Anne Morris, Louise Coke, Grace Hindle, Eirini Kolokouri, Catherine Wright, Claire Lee, Nicola Ward, Adele Dann, Melanie Lockett, Charlotte Cranfield, Louise Jennings, Ankur Srivastava, Lana Ward, Nouf Jeynes, Poonam Ranga, Praveen Rajasekhar, Lisa Gallagher, Linda Patterson, Jill Ward, Rae Basnett, Judy Murphy, Lauren Parking, Emma Lawson, Stacey Short, David Devadason, Gordon Moran, Neelam Khan, Lauren Tarr, Charmaine Olivia, Jimmy Limdi, Kay Goulden, Asad Javed, Lauren McKenzie, Pradeep Bhandari, Michelle Baker-Moffatt, Joanne Dash, Alison Le Poidevin, Hayley Downe, Lucille Bombeo, Helen Blackman, Alan Wiles, Hannah Bloxham, Jose Dias, Evelyn Nadar, Hollie Curgenven, Jonathan Macdonald, Shona Finan, Faye McMeeken, Misbah Mahmood, Stephanie Shields, John Paul Seenan, Des DeSilva, Susanna Malkakorpi, Rachel Carson, Simon Whiteoak, Kelli Edger-Earley, Luke Vamplew, Sarah Ingram, Sharon Botfield, Fiona Hammonds, Clare James, Tariq Ahmad, Gemma Aspinall, Sarah Hawkins, Suzie Marriott, Clare Redstone, Halina Windak, Ana-Marie Adam, Hannah Mabb, Charles Murray, Cynthia Diaba, Fexy Joseph, Glykeria Pakou, Yvonne Gleeson, James Berrill, Natalie Stroud, Carla Pothecary, Lisa Roche, Keri Turner, Lisa Deering, Lynda Israel, Evelyn Baker, Sean Cutler, Rina Mardania Evans, Maxine Nash, Georgina Mallison, Anna Roynon, John Gordon, Emma Levell, Silvia Zagalo, Wendy Fraser, Ina Hoad, Nikolaos Kirkineziadis, Richard Russell, Paul Henderson, Margaret Millar, Andrew Fagbemi, Felicia Jennings, Imelda Mayor, Jill Wilson, Christopher Alexakis, Natalia Michalak, John Saunders, Helen Burton, Vanessa Cambridge, Tonia Clark, Charlotte Ekblad, Sarah Hierons, Joyce Katebe, Emma Saunsbury, Rachel Perry, Matthew Brookes, Kathryn Davies, Marie Green, Ann Plumbe, Clare Ormerod, Helen Christensen, Anne Keen, Jonathan Ogor, Alpha Anthony, Emily Newitt, Fiona Trim, Ruth Casey, Katherine Seymour, Edward Fogden, Kalisha Russell, Anne Phillips, Muaad Abdulla, Jeff Butterworth, Colene Adams, Elizabeth Buckingham, Danielle Childs, Alison Magness, Jo Stickley, Nichola Motherwell, Louise Tonks, Hannah Gibson, S Pajak, Caradog Thomas, Elaine Brinkworth, Lynda Connor, Amanda Cook, Tabitha Rees, Rachel Harford, Emma Wesley, Alison Moss, Jacob Lucas, Claire Lorimer, Maria Oleary, Maxine Dixon, Arvind Ramadas, Julie Tregonning, Olaku Okeke, Wendy Jackson, Ioannis Koumoutsos, Viji George, Swapna Kunhunny, Sophie Laverick, Isla Anderson, Sophie Smith, Kamal Patel, Mariam Ali, Hilda Mhandu, Aleem Rana, Katherine Spears, Joana Teixeira, Richard Pollok, Mark Mencias, Abigail Seaward, Jessica Sousa, Nooria Said, Mark Soomaroo, Valentina Raspa, Asha Tacouri, Nicholas Reps, Rebecca Martin, Christian Selinger, Jenelyn Carbonell, Felicia Onovira, Doris Quartey, Alice L'Anson, Andrew Ashworth, Jessica Bailey, Angie Dunn, Zahid Mahmood, Racheal Campbell, Liane Marsh, Monira Rahman, Sarah Davies, Ruth Habibi, Ellen Jessup-Dunton, Teishel Joefield, Reina Layug, Vinod Patel, Joanne Vere, Victoria Turner, Susan Kilroy, Gareth Walker, Stacey Atkins, Jasmine Growdon, Charlotte McNeill, Rachel Cooney, Lillie Bennett, Louise Bowlas, Sharafaath Shariff, Aileen Fraser, Dwayne Punnette, Charlotte Bishop-Hurman, Elizabeth Undrell, Katherine Belfield, Said Din, Catherine Addleton, Marie Appleby, Johanna Brown, Kathleen Holding, Patricia Hooper, John deCaestecker, Olivia Watchorn, Chris Hayward, Susan Inniss, Lucy Pritchard, Karen Rudge, Amanda Carney, Jervoise Andreyev, Caroline Hayhurst, Carol Lockwood, Lynn Osborne, Amanda Roper, Karen Warner, Julia Hindle, Caroline Watt, Kinga Szymiczek, Shameer Mehta, James Bell, William Blad, Lisa Whitley, Durai Dhamaraj, Mark Baker, Elizabeth John Sivamurugan, Mim Evans, Fraser Cummings, Clare Harris, Amy Jones, Liga Krauze, Sohail Rahmany, Michelle Earl, Jenny Vowles, Audrey Torokwa, Mirela Petrova, Andrew Procter, Jo Stanley, Claudia Silvamoniz, Marion Bettey, Amar Wahid, Zoe Morrison, Rhian Thomas-Turner, Louise Yendle, Jennifer Muller, Marcus Mitchell, John Kirkwood, Anna Barnes, Rakesh Chaudhary, Melanie Claridge, Chiara Ellis, Cheryl Kemp, Ogwa Tobi, Jentus Milton, Emma Johnston, Metod Oblak, Jo Godden, Charlie Lees, Debbie Alexander, Kate Covil, Lauranne Derikx, Sryros Siakavellas, Helen Baxter, Scott Robertson, Linda Smith, Beena Poulose, Anne Colemam, Margareta Balint, Gareth Rhys-Jones, Kerrie Johns, Rachel Hughes, Janet Phipps, Abigail Taylor, Catherine MacPhee, Suzanne Brooks, Katie Smith, Linda Howard, Dianne Wood, Ajay Muddu, Laura Barman, Janine Mallinson, Tania Neale, Diana Ionita, Kerry Elliot, Alison Turnball, Iola Thomas, Kelly Andrews, Jonathon Sutton, Caroline Mulvaney Jones, Julia Roberts, Jeannie Bishop

Affiliations

¹ Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
² Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
³ Department of Gastroenterology, St Marks Hospital and Academic Institute, London, UK.
⁴ Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
⁵ Department of Infectious Disease, Imperial College London, London, UK.
⁶ Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.
⁷ Department of Biochemistry, Exeter Clinical Laboratory International, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
⁸ IBD Unit, Department of Gastroenterology, Hull University Teaching Hospitals NHS Trust, Hull, UK.
⁹ Hull York Medical School, University of Hull, Hull, UK.
¹⁰ Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK.
¹¹ Department of Gastroenterology, Royal Free London NHS Foundation Trust, London, UK.
¹² Genetic Mechanisms of Disease Laboratory, The Francis Crick Institute, London, UK.
¹³ Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.
¹⁴ Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
¹⁵ School of Immunology & Microbial Sciences, King's College London, London, UK.
¹⁶ Department of Gastroenterology, Western General Hospital, NHS Lothian, Edinburgh, UK.
¹⁷ Centre for Inflammation Research, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK.
¹⁸ Department of Gastroenterology, Royal London Hospital, Barts Health NHS Trust, London, UK.
¹⁹ Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK.
²⁰ Department of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
²¹ Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
²² Institute of Genetic and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
²³ Lung Division, Royal Brompton Hospital and Harefield Hospitals, London, UK.
²⁴ Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK. [email protected].
²⁵ Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK. [email protected].

^# Contributed equally.

Abstract

Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 - 27.5] vs 47.6 days [45.5 - 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p <0.0001; 35.9 days [34.9 - 36.8] vs 58.0 days [55.0 - 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal, Humanized / therapeutic use
BNT162 Vaccine
COVID-19 Vaccines
COVID-19*
ChAdOx1 nCoV-19
Humans
Inflammatory Bowel Diseases* / drug therapy
Infliximab / therapeutic use
SARS-CoV-2
T-Lymphocytes
Tumor Necrosis Factor Inhibitors
Viral Vaccines*

Substances

Antibodies, Monoclonal, Humanized
COVID-19 Vaccines
Tumor Necrosis Factor Inhibitors
Viral Vaccines
vedolizumab
ChAdOx1 nCoV-19
Infliximab
BNT162 Vaccine

Abstract

Publication types

MeSH terms

Substances

Grants and funding