Pneumococcus infection Infections and Infestations
Conditions
Interventions
A human challenge study to establish an SPN3 EHPC model, consisting of two parts. The first part is a dose-ranging and safety study whereby sequential cohorts of 10 healthy participants are challenged
Sponsors
Liverpool School of Tropical Medicine
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy young adults aged 18-50 years (inclusive). This age range minimises the risk of invasive pneumococcal infection and allows comparison with previously published experimental work done by our group. 2. Fluent spoken English - to ensure a comprehensive understanding of the research project and their proposed involvement, enabling valid consent to be given 3. Access to their own mobile telephone - to ensure safety and timely communication 4. Capacity to give informed consent
Exclusion criteria
Exclusion criteria: 1. Currently involved in another study unless observational or non-interventional, excluding the EHPC bronchoscopy study (at the discretion of the study team). This is to ensure no harm comes to the participants through over-sampling. 2. Participant in any previous EHPC trial in the past year 3. Participant in previous EHPC trial inoculated with SPN3 in the last 3 years 4. Participant in EHPC Pneumo 2 trial 5. Vaccination: previous pneumococcal vaccination PPV23 or PCV13 (routine in babies born in the UK since 2005) or PCV10. This can be self-reported or confirmed from GP questionnaire (GPQ) if deemed necessary at clinician discretion. 6. Allergy to penicillin/amoxicillin 7. Health history (self-reported or confirmed by GPQ or medical summary if felt to be necessary at clinician discretion): 8. Chronic ill health including immunosuppressive history, diabetes, asthma (on regular medication), recurrent otitis media or other respiratory disease 9. Medication that may affect the immune system e.g., steroids, inflammation altering or disease-modifying anti-rheumatoid drugs 10. Long term use of antibiotics for chronic infection 11. Major pneumococcal illness requiring hospitalisation in the last 10 years 12. Other conditions considered by the clinical team as a concern for participant safety or integrity of the study 13. Significant mental health problems (uncontrolled condition or requiring previous admission to a psychiatric unit) that would impair ability to participate 14. Direct caring role or close contact with individuals at higher risk of infection during the inoculation period if personal protective equipment (PPE) not worn: 14.1. Children under 5 years of age 14.2. Adults with chronic ill health or immunosuppression 14.3. Hospital patients 15. Current or ex-smoker (daily cigarettes, daily e-cigarettes/vaping and daily smoking of recreational drugs) in the last 6 months. Participants who smoke 20 cigarettes per day for 20 years or equivalent [>20 pack years]) 17. Biologically female participants of child-bearing potential (WOCBP) who are: 17.1. Currently pregnant/lactating 17.2. Intending on becoming pregnant during the study 17.3. Not deemed to have effective birth control 18. History of or current drug or alcohol abuse: 18.1. Men should not drink >3 units/day regularly 18.2. Women should not drink >2 units/day regularly 19. Overseas travel planned in follow up period of study visits 20. Natural SPN3 colonisation in baseline nasal wash – if a participant is colonised with non-SPN3 pneumococcus, they can be included as part of exploratory analyses, but would not be included in the primary analysis 21. STOP criteria – participants who meet STOP criteria at the time of screening: 21.1. Clinical history and examination: STOP if unexplained or concerning findings on history or examination 21.2. Severe adverse event (SAE) or research-related injury (RRI): STOP if related SAE or RRI reported 21.3. Engagement with research team: STOP if the research team have concerns about the participant’s ability to commit to frequent communication and safety checks 21.4. Full blood count (FBC): 21.5.1. STOP if Hb 12 x 10e9/l 21.5.4. STOP if platelets <75 x 10e9/l 21.6. Resting SpO2: STOP if <94% 21.7. Illness during the study: STOP if participant develops a me
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The occurrence of experimental SPN3 colonisation of the nasopharynx, determined by SPN3 presence in classical microbiology culture in at least one nasal wash (NW) sample at any timepoint following inoculation(s) (combined and individually), e.g. day 2, day 7, day 13, day 16, day 21 or day 28. This will be assessed for each isolate and dose separately. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The rate of occurrence of SPN3 experimental colonisation determined by classical culture and qPCR (combined and individually) from at least one nasal wash (NW) sample at any time point following one or two inoculations (combined and individually), e.g. day 2, day 7, day 13, day 16, day 21 or day 28. This will be assessed for each isolate and dose separately. 2. The bacterial density of experimental SPN3 colonisation of the nasopharynx in NW determined by classical culture and molecular methods at each and any timepoint following one or two inoculations (combined and individually), e.g. day 2, day 7, day 13, day 16, day 21 or day 28. This will be assessed for each isolate and dose separately. 3. The duration of experimental SPN3 colonisation of nasopharynx determined by the last NW sample following one or two inoculations (combined and individually) i.e. day 13 and/or day 28 in which SPN3 is detected by classical culture or molecular methods. This will be assessed for each isolate and dose separately 4. The presence of mild or moderate symptoms as recorded on a Likert scale in participants with SPN3 within the first 7 days after inoculations. Sore throat grading score will also be used if applicable 5. Cell immunophenotyping using flow cytometry methods to identify and characterise cell populations such as neutrophils, monocytes, T cells and B cells in nasal cells samples at screening and 2, 7, 16, 21 and 28 days after the first inoculation 6. Anti-SPN3 polysaccharide specific immunoglobulin G (IgG) levels measured using ELISA on serum and nasal wash samples taken on days 2, 7 ,13, 16, 21 and 28 7. Quantification and characterization of the number of SPN3-polysaccharide specific memory B cell populations in PBMC samples using flow cytometry methods at screening, 13 and 28 days after the first inoculation 8. 30 cytokines and chemokines measured using multiplex Luminex in nasosorption samples at screening and 2, 7, 13, 16, 21 and 28 days after the first inoculation | — |
Countries
England, United Kingdom
Outcome results
None listed