VIP Study: SARS-CoV2 Vaccine Immunogenicity in immunosuppressed IBD Patients

Summary

SARS-CoV2 infection has caused a global health emergency and has killed 1 in a 1000 of the British population. Vaccination holds the key to protecting individuals and limiting viral transmission at a population level.

Despite the optimism generated by the phase III SARS-CoV2 vaccination studies, there are important knowledge gaps, particularly regarding some of the most vulnerable members of society.

None of the vaccines have been tested in patients taking immunosuppressive drugs. Not only are these patients at high risk of COVID-19 disease, but the immunosuppressive drugs that they take might compromise the ability of vaccines to stimulate protective immune responses. This important knowledge gap could have grave implications for millions of immunosuppressed patients across the globe, who would remain unprotected from SARS-CoV2 infection even after vaccination. 

Inflammatory bowel disease (IBD), comprising Crohn’s disease and ulcerative colitis affect about 620,000 patients in the UK. IBD patients are typically maintained on long-term immunosuppressive drugs to control their disease. Unfortunately, some of these drugs hamper the development of protective immunity following vaccination, at least with currently used vaccines, such as the flu jab.

The purpose of this study is to determine whether different immunosuppressive drugs used to treat IBD reduce the ability of IBD patients to mount durable, protective immune responses after SARS-CoV2 vaccination.

Study Update: The study team would like to thank all BioResource volunteers who took part in this study. Please see the resulting scientific papers published in The Lancet in the links below.

Alexander, James L et al. “COVID-19 vaccine-induced antibody responses in immunosuppressed patients with inflammatory bowel disease (VIP): a multicentre, prospective, case-control study.” The lancet. Gastroenterology & hepatology vol. 7,4 (2022): 342-352.

Alexander, James L et al. “COVID-19 vaccine-induced antibody and T-cell responses in immunosuppressed patients with inflammatory bowel disease after the third vaccine dose (VIP): a multicentre, prospective, case-control study.” The lancet. Gastroenterology & hepatology, S2468-1253(22)00274-6. 8 Sep. 2022.

The VIP study (SARS-CoV2 Vaccination immunogenicity in Immunosuppressed inflammatory bowel disease Patients) investigated antibody responses to COVID-19 (SARS-CoV-2) vaccination, with mRNA (e.g. Pfizer and Moderna) and Adenovirus vector (e.g. Oxford/Astra-Zeneca) vaccines, in patients receiving the full breadth of immunosuppressive therapy types used in inflammatory bowel disease (IBD).

The study was conducted at six research centres across the UK;  Imperial College London, London North West, Barts Health, Cambridge, Edinburgh (NHS Lothian) and Exeter (Royal Devon and Exeter Hospital). Three additional London sites (Guy’s and St Thomas’, King’s College and St George’s) contributed participants to the study. VIP recruited nearly 600 patients (including NIHR Bioresource patients)  who donated blood samples and ‘completed a patient reported questionnaire’ over two study visits from May  2021 to March 2022. The blood samples were analysed for vaccine-induced antibodies (at the Royal Devon and Exeter Hospital) and T cell responses (at Imperial College London) against SARS-CoV-2.

The VIP study key findings are:

• All groups of immunosuppressed patients with IBD had a significant boost in vaccine-induced antibody levels after a third dose of COVID-19 vaccine.
• COVID -19 antibody response after the second and third vaccine doses were lower in patients treated with tofacitinib and infliximab compared to healthy controls (people who don’t have IBD and aren’t on immunosuppressive therapy).
• No significant reduction in antibodies was seen in vedolizumab, ustekinumab or thiopurine-treated patients compared to healthy controls.
• Prior COVID-19 infection and younger age were associated with higher antibody levels.
• T cell responses were similar in all groups, except for recipients of tofacitinib without evidence of previous infection, where T cell responses were significantly reduced relative to healthy controls.

These results represent good news for immunosuppressed patients with IBD because a third dose of COVID-19 vaccine induced a boost in antibody levels in all treatment groups. However, responses were reduced in patients taking infliximab, infliximab/thiopurine combination and tofacitinib. Tofacitinib was also associated with reduced T cell responses. These findings support continued prioritisation of immunosuppressed groups for further booster dosing, particularly those patients taking anti-TNF (e.g. infliximab) and Janus Kinase (JAK) inhibitors (e.g. tofacitinib).