Human co-infection challenge study of S. pneumoniae (Spn) and live attenuated influenza vaccine Infections and Infestations
Conditions
Interventions
Design
This will be a single-blind randomised controlled human co-infection study using a previously established pneumococcal and LAIV infection model. Eligible healthy, older adults will receive an i
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Participant is willing and able to give informed consent for participation in the study 2. Healthy adults, ages as specified depending on study group 3. In the Investigator’s opinion, is able and willing to comply with all study requirements 4. Fluent spoken English – to ensure a comprehensive understanding of the research study 5. Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study. 6. Agreement to provide their National Insurance/Passport number for the purposes of TOPS registration and for payment of reimbursement expenses. 7. Females of childbearing potential* with a negative urine pregnancy test at screening and willing to practice adequate contraceptive** measures as per UK Clinical Trial Facilitation Group during the study 8. Participant must live near to study site or in the surrounding area
Exclusion criteria
Exclusion criteria: The participant may not enter the study if ANY of the following apply: 1. 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 comorbidities are allowed). Including but not limited to: 1.1. Asplenia or dysfunction of the spleen 1.2. Chronic respiratory disease (e.g. asthma [requiring medication (including salbutamol inhaler) within last 12 months], COPD, bronchiectasis and sleep apnoea) 1.3. Chronic heart disease (e.g. angina, ischaemic heart disease, chronic heart failure) – controlled and stable hypertension may be included 1.4. Severe chronic kidney disease (e.g. nephrotic syndrome, kidney transplant, requires dialysis) 1.5. Chronic liver disease (e.g. cirrhosis, biliary atresia, hepatitis) 1.6. Chronic neurological disease that limits mobility, bulbar or respiratory function (including stroke, Parkinson’s disease, dementia and multiple sclerosis) 1.7. Diabetes mellitus (including diet-controlled) 2. Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 12 months or long-term systemic corticosteroid, Roaccutane, or disease modifying anti-rheumatoid drugs therapy (for more than 7 consecutive days within the 3 months prior to enrolment) 3. Individuals with cochlear ear implants 4. Individuals with major cerebrospinal fluid leaks (e.g. following traumatic, major skull surgery, or requiring CSF shunts) 5. Subjects with known or suspected immune deficiency (e.g. known IgA deficiency, immotile cilia syndrome, or Kartagener’s syndrome) 6. History of frequent nose bleeds 7. Bleeding disorders 8. No major pneumococcal illness requiring hospitalisation in the last 10 years 9. Maternal (Group B) 10. Female participants who are pregnant 11. Female participants who are lactating 12. Female participants who intend to become pregnant during the study 13. Female participants unable to take contraception measures during the study (from consent to final study visit) 14. Close contact with individuals at increased risk of pneumococcal disease (eg. children under 5 years, immunocompromised individuals 15. Healthcare workers 16. On medication that may affect the immune system in any way eg. steroids 17. Taking long term antibiotics, nasal/inhaled steroids, oral antiplatelets or warfarin therapy 18. Allergy to penicillin, amoxicillin, gentamicin, gelatin, lidocaine or any ingredient of the influenza vaccine 19. Current regular smoker/vaper (smokes daily) or previous regular smoker/vaper than has stopped smoking/vaping less than 12 months ago (up to 10 pack-years smoking history allowed) 20. History of drug or alcohol abuse (frequently drinking over the recommended alcohol intake limit: men and women should not regularly drink more than 14 units per week) 21. Any clinically significant finding on screening investigation bloods 22. Not able to make specific inoculation/vaccination visit dates required for the study, or overseas travel booked for 21 days following baseline testing 23. Received any influenza vaccine in the same winter season as they are recruited 24. Pneumococcal vaccination (which we can confirm is not the PCV vaccine) in the last 1 year (older adults who have had pneumococcal vaccination but not influenza may be considered for Group B – LAIV only) 25. Participants who have r
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The absence of SAEs/AESIs relating to inoculation throughout the study will be measured by clinical monitoring at D28 in Group A and D31 in Group B | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The absence of SAEs/AESIs relating to inoculation throughout the study will be measured by clinical monitoring at D28 in Group A and D31 in Group B 2. Colonisation risk, density, and duration quantification of secondary Spn6B carriage will be measured by classical culture and molecular methods, including RT-qPCR, 3-5 days after the final visit (Group A: D31-33, Group B: D34-36) 3. Secondary LAIV infection and viral load will be determined by RT-qPCR, 3-5 days after the final visit (Group A: D31-33, Group B: D34-36) 4. Detection of the most common respiratory viruses and other respiratory bacteria will be assessed by microfluidic qPCR, 3-5 days after the final visit (Group A: D31-33, Group B: D34-36) 5. Changes in cell populations, including antigen-specific T and B cells in the nasal mucosa, will be analyzed at different time points, 3-5 days after the final visit (Group A: D31-33, Group B: D34-36) | — |
Countries
England, United Kingdom
Contacts
Public ContactJodie Boyle
Outcome results
None listed