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): a prospective, multicentre, cohort study.

Liu, Zhigang; Alexander, James L; Le, Kaixing; Zhou, Xin; Ibraheim, Hajir; Anandabaskaran, Sulak; Saifuddin, Aamir; Lin, Kathy Weitung; McFarlane, Leon R; Constable, Laura; Seoane, Rocio Castro; Anand, Nikhil; Bewshea, Claire; Nice, Rachel; D'Mello, Andrea; Jones, Gareth R; Balarajah, Sharmili; Fiorentino, Francesca; Sebastian, Shaji; Irving, Peter M; Hicks, Lucy C; Williams, Horace Rt; Kent, Alexandra J; Linger, Rachel; Parkes, Miles; Kok, Klaartje; Patel, Kamal V; Teare, Julian P; Altmann, Daniel M; Boyton, Rosemary J; Hart, Ailsa L; Lees, Charlie W; Goodhand, James R; Kennedy, Nicholas A; Pollock, Katrina M; Ahmad, Tariq; Powell, Nick

Liu, Zhigang; Alexander, James L; Le, Kaixing; Zhou, Xin; Ibraheim, Hajir; Anandabaskaran, Sulak; Saifuddin, Aamir; Lin, Kathy Weitung; McFarlane, Leon R; Constable, Laura; Seoane, Rocio Castro; Anand, Nikhil; Bewshea, Claire; Nice, Rachel; D'Mello, Andrea; Jones, Gareth R; Balarajah, Sharmili; Fiorentino, Francesca; Sebastian, Shaji; Irving, Peter M; Hicks, Lucy C; Williams, Horace Rt; Kent, Alexandra J; Linger, Rachel; Parkes, Miles; Kok, Klaartje; Patel, Kamal V; Teare, Julian P; Altmann, Daniel M; Boyton, Rosemary J; Hart, Ailsa L; Lees, Charlie W; Goodhand, James R; Kennedy, Nicholas A; Pollock, Katrina M; Ahmad, Tariq; Powell, Nick.

Afiliação

Liu Z; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Alexander JL; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Le K; Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK.
Zhou X; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Ibraheim H; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Anandabaskaran S; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Saifuddin A; Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK.
Lin KW; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
McFarlane LR; Department of Gastroenterology, St Marks Hospital and Academic Institute, Gastroenterology, London, UK.
Constable L; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Seoane RC; Department of Gastroenterology, St Marks Hospital and Academic Institute, Gastroenterology, London, UK.
Anand N; Department of Infectious Disease, Imperial College London, London, UK.
Bewshea C; Department of Infectious Disease, Imperial College London, London, UK.
Nice R; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
D'Mello A; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Jones GR; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Balarajah S; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
Fiorentino F; Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK.
Sebastian S; Department of Clinical Chemistry, Exeter Clinical Laboratory International, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK.
Irving PM; Division of Medicine & Integrated Care, Imperial College Healthcare NHS Trust, London, UK.
Hicks LC; Department of Gastroenterology, Western General Hospital, NHS Lothian, Edinburgh, UK.
Williams HR; Centre for Inflammation Research, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK.
Kent AJ; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Linger R; Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK.
Parkes M; Department of Surgery and Cancer, Imperial College London, London, UK.
Kok K; Nightingale-Saunders Clinical Trials & Epidemiology Unit (King's Clinical Trials Unit), King's College London, London, UK.
Patel KV; Department of Gastroenterology, Hull University Teaching Hospitals NHS Trust, Hull, UK.
Teare JP; Hull York Medical School, University of Hull, Hull, UK.
Altmann DM; Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Boyton RJ; School of Immunology & Microbial Sciences, King's College London, London, UK.
Hart AL; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Lees CW; Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK.
Goodhand JR; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Kennedy NA; Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK.
Pollock KM; Department of Gastroenterology, King's College Hospital, London, UK.
Ahmad T; The NIHR Bioresource, University of Cambridge, Cambridge, UK.
Powell N; The NIHR Bioresource, University of Cambridge, Cambridge, UK.

EClinicalMedicine ; 64: 102249, 2023 Oct.

Article em En | MEDLINE | ID: mdl-37842172

ABSTRACT

ABSTRACT

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.