The 'Experimental Human Pneumococcal challenge' (EHPC) model is a way of putting drops of bacteria into the nose. Investigators have studied this model of putting bacteria in the nose safely in over 1500 volunteers over the past decade with no serious side effects and now want to test the model using a different strain of the bacteria that is commonly found in the community, SPN3.

The aim of this study is to determine how much pneumococcus is needed to achieve nasal colonisation and how long the bacteria live in the nose for before natural immune responses eradicate them. By doing this, Investigators will then be able to test how well future vaccines prevent colonisation with pneumococcus. Investigators want to learn more about how the immune system responds to nasal colonisation with pneumococcus, again to help with development of new vaccines.

In this study, investigators propose to determine the optimal dose and isolate of SPN3 to establish colonisation in the human nasopharynx, as well as improving knowledge of immune responses to SPN3 colonisation. The results from this study will be used to inform development of improved SPN3 vaccines and to inform design of future pneumococcal vaccine RCTs.

To increase the relevance of the EHPC model and its use for assessing future vaccines such as V114, investigators are proposing here to set up an EHPC model with carefully selected non-proprietary SPN3 strains. Investigators will conduct a safety and dose-ranging study to determine the optimum SPN3 strain and dose for colonisation acquisition and confirm the dose in a subsequent larger cohort in a reproducibility study and will study mucosal and systemic immune responses to this serotype and their association with protection against colonisation acquisition and clearance.

Inclusion Criteria:• 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.

• Fluent spoken English - to ensure a comprehensive understanding of the research project and their proposed involvement, enabling valid consent to be given.
• Access to their own mobile telephone - to ensure safety and timely communication.
• Capacity to give informed consent.

Exclusion Criteria:

• o 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.

  • Participant in any previous EHPC trial in past year

  • Participant in previous EHPC trial inoculated with SPN3 in the last 3 years

  • Participant in EHPC Pneumo 2 trial

    • 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.
    • Allergy: to penicillin/amoxicillin
    • Health history (self-reported or confirmed by GPQ or medical summary if felt to be necessary at clinician discretion):

  • Chronic ill health including immunosuppressive history, diabetes, asthma (on regular medication), recurrent otitis media or other respiratory disease.

  • Medication that may affect the immune system e.g., steroids, inflammation altering or disease-modifying anti-rheumatoid drugs.

  • Long term use of antibiotics for chronic infection.

  • Major pneumococcal illness requiring hospitalisation in the last 10 years.

  • Other conditions considered by the clinical team as a concern for participant safety or integrity of the study

  • Significant mental health problems (uncontrolled condition or requiring previous admission to a psychiatric unit) that would impair ability to participate

    • Direct caring role or close contact with individuals at higher risk of infection during the inoculation period if personal protective equipment (PPE) not worn:

  • Children under 5 years age

  • Adults with chronic ill health or immunosuppression

  • Hospital patients

    • Smoker:

  • Current or ex-smoker (daily cigarettes, daily e-cigarettes/vaping and daily smoking of recreational drugs) in the last 6 months. Participants who smoke <5 cigarettes per week may be included.

  • Previous significant smoking history (>20 cigarettes per day for 20 years or equivalent [>20 pack years]).

    • Biologically female participants of child-bearing potential (WOCBP) who are:

  • Currently pregnant/lactating

  • Intending on becoming pregnant during the study

  • Not deemed to have effective birth control

    • History of or current drug or alcohol abuse:

  • Men should not drink >3 units/day regularly

  • Women should not drink >2 units/day regularly

    • Overseas travel planned in follow up period of study visits
    • Natural SPN 3 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
    • STOP criteria - participants who meet STOP criteria at time of screening (Table 3) 6.3 Temporary Exclusion Criteria
    • Ongoing COVID-19 symptoms (fever, cough, shortness of breath, anosmia or ageusia) or confirmed current COVID-19 infection. Participants with resolved COVID-19 after their UKHSA determined isolation period has ended can be included.
    • Current/acute illness within 14 days prior to inoculation if COVID-19 negative
    • Positive COVID-19 swab whether symptomatic or asymptomatic within 10 days of inoculation
    • Currently isolating following exposure to COVID-19 as per UKHSA guidance
    • Antibiotic use within 28 days of inoculation.
    • Participants who have been temporarily excluded at screening may be re-screened at a later date to assess their eligibility at this time for inclusion into the study. At this point, the participant would be re-consented if their initial written consent was given >4 months prior to this date.
    • Vaccination 21 days prior to inoculation