TY - JOUR
T1 - Neutralising antibody responses against SARS-CoV-2 Omicron BA.4/5 and wild-type virus in patients with inflammatory bowel disease following three doses of COVID-19 vaccine (VIP)
T2 - a prospective, multicentre, cohort study
AU - VIP study investigators
AU - Liu, Zhigang
AU - Alexander, James L.
AU - Le, Kaixing
AU - Zhou, Xin
AU - Ibraheim, Hajir
AU - Anandabaskaran, Sulak
AU - Saifuddin, Aamir
AU - Lin, Kathy Weitung
AU - McFarlane, Leon R.
AU - Constable, Laura
AU - Seoane, Rocio Castro
AU - Anand, Nikhil
AU - Bewshea, Claire
AU - Nice, Rachel
AU - D'Mello, Andrea
AU - Jones, Gareth R.
AU - Balarajah, Sharmili
AU - Fiorentino, Francesca
AU - Sebastian, Shaji
AU - Irving, Peter M.
AU - Hicks, Lucy C.
AU - Williams, Horace RT
AU - Kent, Alexandra J.
AU - Linger, Rachel
AU - Parkes, Miles
AU - Kok, Klaartje
AU - Patel, Kamal V.
AU - Teare, Julian P.
AU - Altmann, Daniel M.
AU - Boyton, Rosemary J.
AU - Hart, Ailsa L.
AU - Lees, Charlie W.
AU - Goodhand, James R.
AU - Kennedy, Nicholas A.
AU - Pollock, Katrina M.
AU - Ahmad, Tariq
AU - Powell, Nick
AU - Chukwurah, Ijeoma
AU - Haq, Sulaimaan
AU - Lo, Jonathan
AU - Shah, Parita
AU - Wilken-Smith, Stephanie
AU - Ramanathan, Anitha
AU - Patel, Mikin
AU - Romanczuk, Lidia
AU - King, Rebecca
AU - Domingo, Jason
AU - Shamtally, Djamila
AU - Mendoza, Vivien
AU - Barnes, Anna
N1 - Funding Information:
Pfizer.VIP is an investigator-led UK National Institute for Health Research COVID-19 study. Pfizer Ltd provided financial support for the VIP study as an independent research grant. This research was supported by the NIHR Biomedical Research Centres in Imperial College London and Imperial College Healthcare NHS Trust and Cambridge (BRC-1215-20014) and the NIHR Clinical Research Facility Cambridge. The NIHR IBD BioResource supported recruitment to this study. The NIHR Exeter Clinical Research Facility that supported this project is a partnership between the University of Exeter Medical School College of Medicine and Health and Royal Devon University Healthcare NHS Foundation Trust. JLA is a recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-502), funded by Imperial College London and The Joyce and Norman Freed Charitable Trust. GRJ is supported by a Wellcome Trust Clinical Research Career Development Fellowship (220725/Z/20/Z). RJB and DMA are supported by UK Research and Innovation (MR/S019553/1, MR/R02622X/1, MR/V036939/1, and MR/W020610/1), the NIHR Imperial Biomedical Research Centre Institute of Translational Medicine & Therapeutics, the Cystic Fibrosis Trust Strategic Research Centre (2019SRC015), NIHR Efficacy and Mechanism Evaluation Fast Track (NIHR134607), NIHR Long Covid (COV-LT2-0027), Innovate UK (SBRI 10008614), and Horizon 2020 Marie Skłodowska-Curie Innovative Training Network European Training Network (number 860325).
Funding Information:
VIP is an investigator-led UK National Institute for Health Research COVID-19 study. Pfizer Ltd provided financial support for the VIP study as an independent research grant. This research was supported by the NIHR Biomedical Research Centres in Imperial College London and Imperial College Healthcare NHS Trust and Cambridge (BRC- 1215-20014 ) and the NIHR Clinical Research Facility Cambridge. The NIHR IBD BioResource supported recruitment to this study. The NIHR Exeter Clinical Research Facility that supported this project is a partnership between the University of Exeter Medical School College of Medicine and Health and Royal Devon University Healthcare NHS Foundation Trust . JLA is a recipient of an NIHR Academic Clinical Lectureship ( CL-2019-21-502 ), funded by Imperial College London and The Joyce and Norman Freed Charitable Trust . GRJ is supported by a Wellcome Trust Clinical Research Career Development Fellowship ( 220725/Z/20/Z ). RJB and DMA are supported by UK Research and Innovation ( MR/S019553/1 , MR/R02622X/1 , MR/V036939/1 , and MR/W020610/1 ), the NIHR Imperial Biomedical Research Centre Institute of Translational Medicine & Therapeutics, the Cystic Fibrosis Trust Strategic Research Centre ( 2019SRC015 ), NIHR Efficacy and Mechanism Evaluation Fast Track ( NIHR134607 ), NIHR Long Covid ( COV-LT2-0027 ), Innovate UK ( SBRI 10008614 ), and Horizon 2020 Marie Skłodowska-Curie Innovative Training Network European Training Network (number 860325 ).
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/10
Y1 - 2023/10
N2 - Background: Patients with inflammatory bowel disease (IBD) receiving anti-TNF and JAK-inhibitor therapy have attenuated responses to COVID-19 vaccination. We aimed to determine how IBD treatments affect neutralising antibody responses against the Omicron BA.4/5 variant. Methods: In this multicentre cohort study, we prospectively recruited 340 adults (69 healthy controls and 271 IBD) at nine UK hospitals between May 28, 2021 and March 29, 2022. The IBD study population was established (>12 weeks therapy) on either thiopurine (n = 63), infliximab (n = 45), thiopurine and infliximab combination therapy (n = 48), ustekinumab (n = 45), vedolizumab (n = 46) or tofacitinib (n = 24). Patients were excluded if they were being treated with any other immunosuppressive therapies. Participants had two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccines, followed by a third dose of either BNT162b2 or mRNA1273. Pseudo-neutralisation assays against SARS-CoV-2 wild-type and BA.4/5 were performed. The half maximal inhibitory concentration (NT50) of participant sera was calculated. The primary outcome was anti-SARS-CoV-2 neutralising response against wild-type virus and Omicron BA.4/5 variant after the second and third doses of anti-SARS-CoV-2 vaccine, stratified by immunosuppressive therapy, adjusting for prior infection, vaccine type, age, and interval between vaccination and blood collection. This study is registered with ISRCTN (No. 13495664). Findings: Both heterologous (first two doses adenovirus vaccine, third dose mRNA vaccine) and homologous (three doses mRNA vaccine) vaccination strategies significantly increased neutralising titres against both wild-type SARS-CoV-2 virus and the Omicron BA.4/5 variant in healthy participants and patients with IBD. Antibody titres against BA.4/5 were significantly lower than antibodies against wild-type virus in both healthy participants and patients with IBD (p < 0.0001). Multivariable models demonstrated that neutralising antibodies against BA.4/5 after three doses of vaccine were significantly lower in patients with IBD on infliximab (Geometric Mean Ratio (GMR) 0.19 [0.10, 0.36], p < 0.0001), infliximab and thiopurine combination (GMR 0.25 [0.13, 0.49], p < 0.0001) or tofacitinib (GMR 0.43 [0.20, 0.91], p = 0.028), but not in patients on thiopurine monotherapy, ustekinumab, or vedolizumab. Breakthrough infection was associated with lower neutralising antibodies against wild-type (p = 0.037) and BA.4/5 (p = 0.045). Interpretation: A third dose of a COVID-19 mRNA vaccine based on the wild-type spike glycoprotein significantly boosts neutralising antibody titres in patients with IBD. However, responses are lower against the Omicron variant BA.4/5, particularly in patients taking anti-TNF and JAK-inhibitor therapy. Breakthrough infections are associated with lower neutralising antibodies and immunosuppressed patients with IBD may receive additional benefit from bivalent vaccine boosters which target Omicron variants. Funding: Pfizer.
AB - Background: Patients with inflammatory bowel disease (IBD) receiving anti-TNF and JAK-inhibitor therapy have attenuated responses to COVID-19 vaccination. We aimed to determine how IBD treatments affect neutralising antibody responses against the Omicron BA.4/5 variant. Methods: In this multicentre cohort study, we prospectively recruited 340 adults (69 healthy controls and 271 IBD) at nine UK hospitals between May 28, 2021 and March 29, 2022. The IBD study population was established (>12 weeks therapy) on either thiopurine (n = 63), infliximab (n = 45), thiopurine and infliximab combination therapy (n = 48), ustekinumab (n = 45), vedolizumab (n = 46) or tofacitinib (n = 24). Patients were excluded if they were being treated with any other immunosuppressive therapies. Participants had two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccines, followed by a third dose of either BNT162b2 or mRNA1273. Pseudo-neutralisation assays against SARS-CoV-2 wild-type and BA.4/5 were performed. The half maximal inhibitory concentration (NT50) of participant sera was calculated. The primary outcome was anti-SARS-CoV-2 neutralising response against wild-type virus and Omicron BA.4/5 variant after the second and third doses of anti-SARS-CoV-2 vaccine, stratified by immunosuppressive therapy, adjusting for prior infection, vaccine type, age, and interval between vaccination and blood collection. This study is registered with ISRCTN (No. 13495664). Findings: Both heterologous (first two doses adenovirus vaccine, third dose mRNA vaccine) and homologous (three doses mRNA vaccine) vaccination strategies significantly increased neutralising titres against both wild-type SARS-CoV-2 virus and the Omicron BA.4/5 variant in healthy participants and patients with IBD. Antibody titres against BA.4/5 were significantly lower than antibodies against wild-type virus in both healthy participants and patients with IBD (p < 0.0001). Multivariable models demonstrated that neutralising antibodies against BA.4/5 after three doses of vaccine were significantly lower in patients with IBD on infliximab (Geometric Mean Ratio (GMR) 0.19 [0.10, 0.36], p < 0.0001), infliximab and thiopurine combination (GMR 0.25 [0.13, 0.49], p < 0.0001) or tofacitinib (GMR 0.43 [0.20, 0.91], p = 0.028), but not in patients on thiopurine monotherapy, ustekinumab, or vedolizumab. Breakthrough infection was associated with lower neutralising antibodies against wild-type (p = 0.037) and BA.4/5 (p = 0.045). Interpretation: A third dose of a COVID-19 mRNA vaccine based on the wild-type spike glycoprotein significantly boosts neutralising antibody titres in patients with IBD. However, responses are lower against the Omicron variant BA.4/5, particularly in patients taking anti-TNF and JAK-inhibitor therapy. Breakthrough infections are associated with lower neutralising antibodies and immunosuppressed patients with IBD may receive additional benefit from bivalent vaccine boosters which target Omicron variants. Funding: Pfizer.
KW - Breakthrough infection
KW - Inflammatory bowel disease
KW - Infliximab
KW - SARS-CoV-2
KW - Tofacitinib
UR - http://www.scopus.com/inward/record.url?scp=85173722247&partnerID=8YFLogxK
U2 - 10.1016/j.eclinm.2023.102249
DO - 10.1016/j.eclinm.2023.102249
M3 - Article
AN - SCOPUS:85173722247
SN - 2589-5370
VL - 64
JO - EClinicalMedicine
JF - EClinicalMedicine
M1 - 102249
ER -
