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
Authors: Lin Simeng , Kennedy Nicholas A. , Saifuddin Aamir , Sandoval Diana Muñoz , Reynolds Catherine J. , Seoane Rocio Castro , Kottoor Sherine H. , Pieper Franziska P. , Lin Kai-Min , Butler David K. , Chanchlani Neil , Nice Rachel , Chee Desmond , Bewshea Claire , Janjua Malik , McDonald Timothy J. , Sebastian Shaji , Alexander James L. , Constable Laura , Lee James C. , Murray Charles D. , Hart Ailsa L. , Irving Peter M. , Jones Gareth-Rhys , Kok Klaartje B. , Lamb Christopher A. , Lees Charlie W. , Altmann Daniel M. , Boyton Rosemary J. , Goodhand James R. , Powell Nick , Ahmad Tariq ,   CLARITY IBD study, Kok Klaartje B. , Bokth Farjhana , Cipriano Bessie , Francia Caroline , Khalid Nosheen , Khatun Hafiza , Kingston Ashley , Lee Irish , Lehmann Anouk , Naik Kinnari , Pabriaga Elise , Plaatjies Nicolene , Samuels Kevin , Saich Rebecca , Cousins Hayley , Fraser Wendy , Thomas Rachel , Brown Matthew , White Benjamin , Kirkineziadis Nikolaos , Tilley Bernadette , Muhammed Rafeeq , Bi Rehana , Cotter Catherine , Grove Jayne , Hong Kate , Howman Ruth , Mitchell Monica , Clayton Sophie , Sultan Sugrah , Rooney Melanie , Cottrill Charlotte , Singh Salil , Dawe Chris , Hull Robert , Silva Natalie , Manning Jonathan , Finlayson Lauren , Roebuck Allison , Dawson Joy , Sonwalkar Sunil , Chambers Naomi , Robinson Matthew , Haigh Andrew , Matapure Lear , Raine Tim , George Varun , Kapizioni Christina , Strongili Konstantina , Thompson Tina , Ahmed Mohamed , Kontos Christos , Bourges Christophe , Barbutti Isabella , Gozzard Megan E. , Hendy Philip , Bull Rhian , Costa Patricia , Davey Lisa , Hannington Hayley , Nundlall Kribashnie , Martins Catarina , Avanzi Laura , Carungcong Jaime , Barr Sabrina , Appleby Richard , Johnson Emma , Phillis Kath , Gascoyne Rachel , Crowder Amanda , Whileman Amanda , London Ian , Grounds Jenny , Martin Emmeline , Pajak Susie , Price Jude , Cawley Kathryn , Dhar Anjan , Brown Ellen , Cowton Amanda , Stamp Kimberley , Warner Ben , Stuart Carmel , Lacey Louise , de Silva Shanika , Allcock Clare , Harvey Philip , Jones Lesley , Cooke Elise , Brooks Johanne , Baker Pearl , Beadle Hannah , Cruz Carina , Potter Debbie , Collum Joe , Masters Farzana , Kumar Aashish , Coetzee Samantha , Peiu Mihaela , Icke Becky , Raj Meena , Gaynor Edward , Chadokufa Sibongile , Huggett Bonita , Meghari Hamza , El-Khouly Sara , Kiparissi Fevronia , Girshab Waffa , Claridge Andrew , Fowler Emily , McCafferty Laura , Christodoulides Karolina , Clifford Angela , Dawson Patrick , Honap Sailish , Lim Samuel , Luber Raphael , Mahiouz Karina , Meade Susanna , Raymode Parizade , Reynolds Rebecca , Stanton Anna , Tripoli Sherill , Hare Naomi , Balachandran Senthuran , North Emma , North Jessica , Browne Bria , Jameson Ella , Siaw Yih Harn , Manzano Lane , Segal Jonathan , Al-Bakir Ibrahim , Khakoo Imran , Thoua Nora , Davidson Katherine , Miah Jagrul , Canclini Lisa , Hall Alex , Hayes Melony , Myers Sally , Talbot Alison , Turnbull Jack , Whitehead Emma , Stamp Katie , Pattinson Alison , Mathew Verghese , Sherris Leanne , Harvey Angela , Hicks Lucy , Byrne Tara-Marie , Cabreros Leilani , Downing-Wood Hannah , Hunter Sophie , Prabhudev Hemanth , Balarajah Sharmili , Ibraheim Hajir , Torkizadeh Melissa , Lo Jonathan W. , Liu Zhigang , Sutherland Helen , Wilhelmsen Elva , Mackintosh Katherine , Verma Ajay M. , Sebastian Juliemol , Peerally Mohammad Farhad , Raymode Parizade , Guerdette Anne-marie , Kent Alexandra , Choong Lee Meng , Pantaloni Benedetta , Ravdas Pantelis , Vadamalayan Babu , Foley Stephen , Arnold Becky , Heeley Cheryl , Lovegrove Wayne , Sowton Donna , Allsop Lynne , Gregory Heidi , Smith Philip J. , Bretland Giovanna , King Sarah , Lofthouse Martina , Rigby Lindsey , Subramanian Sreedhar , Tyrer David , Martin Kate , Probert Christopher , Kamperidis Nikolaos , Adedoyin Temi , Baden Manisha , Brown Jeannette , Chacko Feba , Cicchetti Michela , Saifuddin Mohammad Aamir , Yesupatham Priya , Gowda Rohit , Williams Maureen , Kemp Karen , Akhand Rima , Gray Glaxy , John Anu , John Maya , Mohammed Tasnim , Sathe Diamond , Jones Natasha , Soren Jennifer , Sprakes Michael , Burton Julie , Kane Patricia , Lupton Stephanie , Bartholomew Jacqueline , MacFaul George , Scaletta Diane , Siamia Loria , Williams Felicity , Green Chloe , Ver Zeljka , Lamb Christopher A. , Doona Mary , Hogg Ashleigh , Jeffrey Lesley , King Andrew , Speight R. Alexander , Doyle Jennifer , Owen Ruth , Mowat Craig , Rice Debbie , MacFarlane Susan , MacLeod Anne , Mohammed Samera , Murray Shona , Elliott Anne , Morris Mary Anne , Coke Louise , Hindle Grace , Kolokouri Eirini , Wright Catherine , Lee Claire , Ward Nicola , Dann Adele , Lockett Melanie , Cranfield Charlotte , Jennings Louise , Srivastava Ankur , Ward Lana , Jeynes Nouf , Ranga Poonam , Rajasekhar Praveen , Gallagher Lisa , Patterson Linda , Ward Jill , Basnett Rae , Murphy Judy , Parking Lauren , Lawson Emma , Short Stacey , Devadason David , Moran Gordon , Khan Neelam , Tarr Lauren , Olivia Charmaine , Limdi Jimmy , Goulden Kay , Javed Asad , McKenzie Lauren , Bhandari Pradeep , Baker-Moffatt Michelle , Dash Joanne , Le Poidevin Alison , Downe Hayley , Bombeo Lucille , Blackman Helen , Wiles Alan , Bloxham Hannah , Dias Jose , Nadar Evelyn , Curgenven Hollie , Macdonald Jonathan , Finan Shona , McMeeken Faye , Mahmood Misbah , Shields Stephanie , Seenan John Paul , DeSilva Des , Malkakorpi Susanna , Carson Rachel , Whiteoak Simon , Edger-Earley Kelli , Vamplew Luke , Ingram Sarah , Botfield Sharon , Hammonds Fiona , James Clare , Ahmad Tariq , Aspinall Gemma , Hawkins Sarah , Marriott Suzie , Redstone Clare , Windak Halina , Adam Ana-Marie , Mabb Hannah , Murray Charles , Diaba Cynthia , Joseph Fexy , Pakou Glykeria , Gleeson Yvonne , Berrill James , Stroud Natalie , Pothecary Carla , Roche Lisa , Turner Keri , Deering Lisa , Israel Lynda , Baker Evelyn , Cutler Sean , Evans Rina Mardania , Nash Maxine , Mallison Georgina , Roynon Anna , Gordon John , Levell Emma , Zagalo Silvia , Fraser Wendy , Hoad Ina , Kirkineziadis Nikolaos , Russell Richard , Henderson Paul , Millar Margaret , Fagbemi Andrew , Jennings Felicia , Mayor Imelda , Wilson Jill , Alexakis Christopher , Michalak Natalia , Saunders John , Burton Helen , Cambridge Vanessa , Clark Tonia , Ekblad Charlotte , Hierons Sarah , Katebe Joyce , Saunsbury Emma , Perry Rachel , Brookes Matthew , Davies Kathryn , Green Marie , Plumbe Ann , Ormerod Clare , Christensen Helen , Keen Anne , Ogor Jonathan , Anthony Alpha , Newitt Emily , Trim Fiona , Casey Ruth , Seymour Katherine , Fogden Edward , Russell Kalisha , Phillips Anne , Abdulla Muaad , Butterworth Jeff , Adams Colene , Buckingham Elizabeth , Childs Danielle , Magness Alison , Stickley Jo , Motherwell Nichola , Tonks Louise , Gibson Hannah , Pajak S. , Thomas Caradog , Brinkworth Elaine , Connor Lynda , Cook Amanda , Rees Tabitha , Harford Rachel , Wesley Emma , Moss Alison , Lucas Jacob , Lorimer Claire , Oleary Maria , Dixon Maxine , Ramadas Arvind , Tregonning Julie , Okeke Olaku , Jackson Wendy , Koumoutsos Ioannis , George Viji , Kunhunny Swapna , Laverick Sophie , Anderson Isla , Smith Sophie , Patel Kamal , Ali Mariam , Mhandu Hilda , Rana Aleem , Spears Katherine , Teixeira Joana , Pollok Richard , Mencias Mark , Seaward Abigail , Sousa Jessica , Said Nooria , Soomaroo Mark , Raspa Valentina , Tacouri Asha , Reps Nicholas , Martin Rebecca , Selinger Christian , Carbonell Jenelyn , Onovira Felicia , Quartey Doris , L’Anson Alice , Ashworth Andrew , Bailey Jessica , Dunn Angie , Mahmood Zahid , Campbell Racheal , Marsh Liane , Rahman Monira , Davies Sarah , Habibi Ruth , Jessup-Dunton Ellen , Joefield Teishel , Layug Reina , Patel Vinod , Vere Joanne , Turner Victoria , Kilroy Susan , Walker Gareth , Atkins Stacey , Growdon Jasmine , McNeill Charlotte , Cooney Rachel , Bennett Lillie , Bowlas Louise , Shariff Sharafaath , Fraser Aileen , Punnette Dwayne , Bishop-Hurman Charlotte , Undrell Elizabeth , Belfield Katherine , Din Said , Addleton Catherine , Appleby Marie , Brown Johanna , Holding Kathleen , Hooper Patricia , deCaestecker John , Watchorn Olivia , Hayward Chris , Inniss Susan , Pritchard Lucy , Rudge Karen , Carney Amanda , Andreyev Jervoise , Hayhurst Caroline , Lockwood Carol , Osborne Lynn , Roper Amanda , Warner Karen , Hindle Julia , Watt Caroline , Szymiczek Kinga , Mehta Shameer , Bell James , Blad William , Whitley Lisa , Dhamaraj Durai , Baker Mark , Sivamurugan Elizabeth John , Evans Mim , Cummings Fraser , Harris Clare , Jones Amy , Krauze Liga , Rahmany Sohail , Earl Michelle , Vowles Jenny , Torokwa Audrey , Petrova Mirela , Procter Andrew , Stanley Jo , Silvamoniz Claudia , Bettey Marion , Wahid Amar , Morrison Zoe , Thomas-Turner Rhian , Yendle Louise , Muller Jennifer , Mitchell Marcus , Kirkwood John , Barnes Anna , Chaudhary Rakesh , Claridge Melanie , Ellis Chiara , Kemp Cheryl , Tobi Ogwa , Milton Jentus , Johnston Emma , Oblak Metod , Godden Jo , Lees Charlie , Alexander Debbie , Covil Kate , Derikx Lauranne , Siakavellas Sryros , Baxter Helen , Robertson Scott , Smith Linda , Poulose Beena , Colemam Anne , Balint Margareta , Rhys-Jones Gareth , Johns Kerrie , Hughes Rachel , Phipps Janet , Taylor Abigail , MacPhee Catherine , Brooks Suzanne , Smith Katie , Howard Linda , Wood Dianne , Muddu Ajay , Barman Laura , Mallinson Janine , Neale Tania , Ionita Diana , Elliot Kerry , Turnball Alison , Thomas Iola , Andrews Kelly , Sutton Jonathon , Jones Caroline Mulvaney , Roberts Julia , Bishop Jeannie 
Published: March 2022

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.