Pneumoccocal carriage Infections and Infestations
Conditions
Interventions
Current interventions as of 10/03/2025:
This is a single-centre, open-label controlled human infection study in older healthy participants using a previously established and safe model of pneumococcal
Sponsors
Liverpool School of Tropical Medicine
Eligibility
Sex/Gender
All
Age
50 Years to 84 Years
Inclusion criteria
Inclusion criteria: 1. Healthy adults aged 50-84 (inclusive, at the time of consent and inoculation) years old 2. World Health Organisation performance status 0 (able to carry out all normal activity without restriction) or 1 (restricted in strenuous activity but ambulatory and able to carry out light work) 3. Access to telephone and e-mail 4. Fluent spoken English – to ensure a comprehensive understanding of the research project 5. Capacity to provide written informed consent in English
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 20/08/2025: Individuals may not participate in the study if they are/have: Research participant: 1. Currently involved in another study unless observational or non-interventional, excluding the EHPC bronchoscopy study (at the discretion of the study team) and exceptions may be applied at the discretion of the CI/PI to ensure no harm comes to the participants (e.g. excessive blood or nasal sampling) 2. Participated in a previous Spn6B/Spn3 EHPC study within 3 years Nasal carriage: Participants who have natural pneumococcal identified at screening Vaccination: 1. Had any vaccination within 28 days of enrolment (defined as the time of inoculation) other than against influenza or COVID-19, which is permissible up to 14 days before inoculation 2. Had a pneumococcal conjugate vaccine* Allergy: Allergy to beta-lactam antibiotics (including penicillin and amoxicillin) Medical history leading to increased risk of severe infection, illness, including but not limited to: 1. Asplenia or dysfunction of the spleen 2. Chronic respiratory disease (e.g. asthma [requiring medication (including salbutamol inhaler) within the last 12 months], COPD, bronchiectasis) 3. Chronic heart disease (e.g. angina, ischaemic heart disease, chronic heart failure) - controlled and stable hypertension may be included 4. Chronic kidney disease (e.g. kidney transplant, regular dialysis, CKD3-5) 5. Chronic liver disease (e.g. cirrhosis, hepatitis) 6. Chronic neurological disease that limits mobility, bulbar or respiratory function (including stroke, Parkinson’s disease, dementia and multiple sclerosis) 7. Diabetes mellitus (including diet controlled) 8. Cancer within the past 5 years (except for basal cell carcinoma of the skin, melanoma in situ and cervical carcinoma in situ) 9. Receipt of immunosuppressive therapy such as anti-cancer immunotherapy, chemotherapy or radiation therapy within the preceding 5 years or long-term systemic corticosteroid, Roaccutane, or disease-modifying anti-rheumatoid drugs therapy (for more than 7 consecutive days within the 3 months before enrolment) 10. Individuals with cochlear ear implants 11. Individuals with major cerebrospinal fluid leaks (e.g. following traumatic, major skull surgery, or requiring CSF shunts) 12. Subjects with known or suspected immune deficiency (e.g. HIV, known IgA deficiency, immotile cilia syndrome, or Kartagener’s syndrome) 13. History of frequent nose bleeds within the last 2 years 14. Bleeding disorders 15. Significant mental health disorders 16. Other uncontrolled comorbidities, as determined by the clinical investigator, which would be expected to increase the risk of pneumococcal disease 17. Any major pneumococcal illness or pneumonia requiring hospitalisation in the last 10 years 18. Meeting STOP criteria Medication: 1. Any medication that may affect the immune system in the last 3 months (e.g. systemic steroids [IM/IV], steroid nasal spray, Roaccutane, disease-modifying anti-rheumatoid drugs) 2. Long-term antibiotic use or any antibiotics (other than topical) in the past 28 days 3. Recipient of monoclonal antibodies in the last 6 months for any indication 4. Recipient of blood transfusion products within the last year 5. Any medication that may affect the coagulation system in the last 3 months (excluding low-dose aspirin) 6. Use of any medication or other product (prescription or over-the-counter) for symptoms of rhinitis or nasal congestion within the last 1 month, ex
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The detection of pneumococcus within nasal epithelial cells, obtained through minimally-invasive superficial nasal scrape biopsies, measured using confocal microscopy and association with nasal colonisation outcome (measured by classical microbiology and multiplex PCR) following pneumococcal inoculation within 28 days from pneumococcal challenge. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 10/03/2025: The following secondary outcome measures are assessed at Day 2, 6, 9, 14 and 28 post pneumococcal challenge: 1. Rates of colonization by pneumococcus and its density and duration by detection of pneumococcus serotype 6B (Phase A) or serotype 3 (Phase B) from one or more nasal wash samples by microbiological culture or multiplex qPCR in the 28 days following the initial pneumococcal challenge 2. Changes in the population of immune/inflammatory cells, specifically innate immune cell dynamics, activation and functionality in the nasal mucosa, in response to challenge and/or colonisation, measured using immunophenotyping on nasal epithelial cell samples 3. Quantification of a systemic and mucosal humoral immune response to nasopharyngeal (NP) carriage by measuring pneumococcal serotype-specific antibodies on nasal and blood samples using ELISAs 4. Quantification of a systemic and mucosal cellular immune response to NP carriage by measuring pneumococcal-specific T-cell recall responses using immunophenotyping 5. Demonstration of functional activity of participant anti-pneumococcal antibodies measured using assays including opsonophagocytic killing assays Previous secondary outcome measures: The following secondary outcome measures are assessed at Day 2, 6, 9, 14 and 28 post pneumococcal challenge: 1. Rates of colonization by pneumococcus and its density and duration by detection of pneumococcus serotype 6B from one or more nasal wash samples by microbiological culture or multiplex qPCR in the 28 days following the initial pneumococcal challenge 2. Changes in the population of immune/inflammatory cells, specifically innate immune cell dynamics, activation and functionality in the nasal mucosa, in response to challenge and/or colonisation, measured using immunophenotyping on nasal epithelial cell samples 3. Quantification of a systemic and mucosal humoral immune response to nasopharyngeal (NP) carriage by measuring pneu | — |
Countries
England, United Kingdom
Contacts
Public ContactDavid Oliver Hamilton
Outcome results
None listed