Why mRNA vaccines do not appear to work as well in older adults and people on specific immunosuppressive medications, such as those for inflammatory bowel disease (IBD) Infections and Infestations
Conditions
Interventions
This is an open-label, observational, experimental medicine study to investigate human immune responses in lymph node cells after immunisation with the COVID-19 mRNA booster vaccine. Participants will
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Age
18 Years to 110 Years
Inclusion criteria
Inclusion criteria: Participants must satisfy all the following criteria to be eligible for the study: 1. Adults aged between 18 to 45 years (inclusive) OR aged 65 years and over OR aged 18 to 50 years on anti-TNF immunosuppressive therapy 2. Medically stable (i.e., according to investigator judgement, it is not anticipated that the participant will require hospitalisation within the study period or that they will need to withdraw from the study for medical reasons before completion of protocol-specified follow-up). A stable medical condition is defined as a disease not requiring significant change in therapy or hospitalisation for worsening disease during the 90 days prior to enrolment. 3. Able to attend the scheduled visits and comply with all study procedures 4. Willing and able to give informed consent for participation in the study 5. Agree to allow study staff to contact his or her GP or equivalent NHS databases to access the participant’s vaccination records, medical history 6. Willing to allow their GP and/or consultant, if appropriate, to be notified of participation in the study 7. Willing to provide their national insurance number or passport number to be registered on The Over-Volunteering Prevention System (TOPS) 8. Agree to refrain from blood donation whilst in the study 9. For participants of childbearing potential only (as defined by protocol Section 8.5): not planning pregnancy during participation in the study and willing to have a negative pregnancy test on the days of screening and study injections 10. Have received at least a primary (two-dose) schedule of any MHRA, UK-authorised or licensed COVID-19 vaccine For Group C participants (participants taking anti-TNF therapy), they would also have to satisfy the following criteria in addition to the above to be eligible for the study: 11. Have a diagnosis of inflammatory bowel disease (Crohn’s disease, ulcerative colitis, or inflammatory bowel disease unclassified) 12. On stable anti-TNF immunosuppressive therapy for the preceding 12 months before enrolment
Exclusion criteria
Exclusion criteria: 1. Participation in another research study involving an investigational product, the receipt or planned receipt of an investigational product, or the donation of significant volumes of blood that could compromise the integrity of this study, either within the 12 weeks prior to enrolment or planned during the study period. 2. Body mass index =35 3. Administration of immunoglobulins and/or any blood products within the three months of study enrolment. 4. Administration of regular anticoagulation medication likely to induce bruising or bleeding on fine needle aspiration. 5. Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; severe infection(s); receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 12 months, or long-term systemic corticosteroid therapy (including for more than 7 consecutive days within the previous 3 months). 6. History of anaphylaxis in relation to vaccination, or local anaesthetic such as lidocaine. 7. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine including hypersensitivity to the active substance or to any of the excipients of the vaccine or to local anaesthetic such as lidocaine. 8. History of cancer that is not resolved (except basal cell carcinoma of the skin and cervical carcinoma in situ). 9. History of any serious psychiatric condition likely to affect participation in the study. 10. For participants of childbearing potential only: participants who are pregnant, breastfeeding or lactating, or are planning pregnancy during the study. 11. History of a bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture. 12. Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, or neurological illness, as judged by the Investigator (note, mild/moderate well-controlled co-morbidities are acceptable). 13. Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units per week. 14. Suspected or known injecting drug use within the 5 years preceding enrolment. 15. Detectable circulating hepatitis B surface antigen (HBsAg). 16. Seropositive for hepatitis C virus (antibodies to HCV). 17. Seropositive for HIV. 18. A history of pericarditis, myocarditis or other cardiac inflammation deemed significant by the investigator. 19. Any clinically significant finding on screening investigations, that are either unlikely to resolve or do not resolve on repeat testing (at the discretion of an Investigator) within the recruitment timeline of the study. 20. Member of the study team. This is deliberately loosely defined, but at a minimum will include: anyone on the delegation log; anyone who might be anticipated to be placed onto the delegation log in the course of the study; anyone who has access to personal data on study participants (beyond name, contact details, DOB); and anyone who attends meetings where details of the study are discussed, for example safety updates. 21. Any confirmed or suspected immunodeficient state unrelated to anti-TNF therapy, including HIV infection; asplenia; anti-cancer chemotherapy or radiation therapy within the preceding 12 months, or long-term systemic corticosteroid thera
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The frequency of GC B cells in the ipsilateral and contralateral LNs post mRNA immunisation in younger adult volunteers compared with those on anti-TNF therapy using single-cell ribonucleic acid sequencing 5-prime (5’ scRNA-seq) at day 14 | — |
Secondary
| Measure | Time frame |
|---|---|
| The frequency of GC B cells in the draining LN post-mRNA immunisation in older people versus healthy controls or individuals on anti-TNF therapy, and the cell signalling pathways active in these cells using single-cell ribonucleic acid sequencing 5-prime (5’ scRNA-seq) at day 14 | — |
Countries
England, United Kingdom
Contacts
Public ContactNelly Owino
Outcome results
None listed