Determining the Relationship Between Gut Microbiota and Immune Response to Influenza or COVID-19 Vaccine

Study Overview
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Brief Summary
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This study will evaluate the effect of the microorganisms in the gut on how well the flu or COVID-19 vaccine works in people who have a weakened immune system due to inflammatory bowel disease. Participants can expect to be in the study for up to 65 days.

Detailed Description
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The overall objective of this study is to evaluate the role of gut microbiome in influenza or COVID-19 vaccine response in immunosuppressed populations. Microbial diversity (alpha diversity) is decreased in immunosuppressed patients and might be associated with lower immunogenicity to vaccines. It is known that patients with IBD have dysbiosis of their gut microbiome and those immunosuppressed may have a lower vaccine response. In this aim, the investigators will evaluate whether differences in microbial diversity predict immune response to the influenza and COVID-19 vaccine. In this prospective study, immunosuppressed IBD patients will be vaccinated per standard of care and blood will be collected to measure the immune response. A fecal and saliva sample will be collected to characterize the gut microbiome. The investigators hypothesize that reduced richness / alpha-diversity in gut microbiota will correlate with those with a blunted vaccine response.

Official Title
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Determining the Relationship Between Gut Microbiota and Immune Response to Influenza or COVID-19 Vaccine in Immunosuppressed Patients With Inflammatory Bowel Disease

Conditions
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Inflammatory Bowel Diseases

Intervention / Treatment
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* Biological: Influenza vaccine
* Biological: COVID-19 vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A history of chronic (greater than 3 month) ulcerative colitis or Crohn's disease diagnosed and documented by the standard clinical, radiographic, endoscopic, and histopathologic criteria Currently one of the following groups: Group A: Anti-TNF Therapy Group - Maintenance monotherapy: infliximab (at least 8 every 8 weeks), golimumab (at least monthly), adalimumab (at least every 2 weeks), or certolizumab (at least monthly) Group B: Non-TNG biologic - Ustekinumab on either ustekinumab monotherapy or combination therapy with methotrexate or azathioprine. Vedolizumab Therapy Group: Vedolizumab Therapy: on either vedolizumab monotherapy or combination therapy with methotrexate or azathioprine Risankizumab Therapy: 360mg every 8 weeks Group C: Janus Kinase Therapy Tofacitinib Therapy Group: on tofacitinib at least 5mg PO BID Upadactinib Therapy Group: on upadactinib at least 15mg PO Patient has been on stable treatment for IBD for at least three months Must be able to provide research samples between 28-65 days post influenza or Covid-19 vaccination. Exclusion Criteria: Member of a vulnerable group (pregnant, lacking consent capacity, non-English speaking) Recent antibiotics within previous 2 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants with Inflammatory Bowel Disease (IBD)<br>Participants with IBD who are receiving a flu or COVID-19 vaccine | Biological: Influenza vaccine<br>* Observe effects of flu vaccine on microbiome<br>Biological: COVID-19 vaccine<br>* Observe effects of COVID-19 vaccine on microbiome<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Influenza or COVID-17 antibody concentrations | Hemagglutination inhibition assay (HIA) will be used to measure influenza antibodies in blood. COVID-19 antibody concentration analysis will be completed with LabCorp's Cov2Quant IgG™ assay which uses immunoassay that uses electrochemiluminescent technology (ECL) for quantitative determination of anti-receptor binding domain (RBD) IgG antibodies specific to SARS-CoV-2. | Baseline | 
| Influenza or COVID-19 antibody concentrations | Hemagglutination inhibition assay (HIA) will be used to measure influenza antibodies in blood. COVID-19 antibody concentration analysis will be completed with LabCorp's Cov2Quant IgG™ assay which uses immunoassay that uses electrochemiluminescent technology (ECL) for quantitative determination of anti-receptor binding domain (RBD) IgG antibodies specific to SARS-CoV-2. | One blood draw between 28-65 days after baseline | 
| Microbiome metrics | Microbiome metrics will include phylogenetic diversity, and analyses of relative abundance of microbes using 16SrRNA gene sequence data from fecal material. Alpha diversity of the microbiome will be evaluated. | One stool collection between days 0-65 | 
| Microbiome stability | Microbiome stability will be evaluated using hierarchical clustering of weighted and unweighted UniFrac distances (a beta diversity metric indexing compositional similarity/difference) for microbiome using 16SrRNA gene sequence data from fecal material. | One stool collection between days 0-65 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between Fecal Metabolomic Activity and Vaccine Response |  | up to 65 days | 
| Correlation between Saliva DNA and Vaccine Response |  | up to 65 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's disease, ulcerative colitis