Carriage to Assess Protection of New Pneumococcal Vaccines - PCV15

Inclusion Criteria:

1. Adults between 18 to 50 years old (inclusive) at the time of enrolment.

2. Medically healthy, such that according to investigator judgement, hospitalisationwithin the study period is not anticipated, and the participant appears likely to beable to remain a study participant through to the end of protocol-specifiedfollow-up. Planned elective procedures for pre-existing conditions may be allowable.

3. Fluent spoken English - to ensure a comprehensive understanding of the researchproject and their proposed involvement.

4. Able to attend the scheduled visits and to comply with all study procedures,including internet access for the recording of electronic diary after inoculation.

5. Willing and able to give informed consent for participation in the study.

6. Willing to allow confirmation of past medical history either through provision of,or access to, a medical record summary or other medical documentation or allowinginvestigators to obtain a copy of their medical history from their GP practice oraccessed via electronic patient records.

7. Willing to allow their GP and/or consultant, if appropriate, to be notified ofparticipation in the study.

8. Willing to provide their national insurance number or passport number to beregistered on The Over-Volunteering Prevention System (TOPS).

9. For participants of childbearing potential only: willing to use effectivecontraception for the duration of the study AND to have a pregnancy test on the dayof screening and challenge.

Exclusion Criteria:

1. Research Participants:

2. Participation in another research study, in which procedures performed couldcompromise the integrity of this study (such as significant volumes of bloodtaken), or are planning to do so within the trial period

3. Currently a participant in a previous EHPC trial within the last 2 years or atthe discretion of the study team

4. Vaccination (self-reported or confirmed from GP questionnaire or medicalrecords/summary if deemed necessary at clinician discretion):

5. Have had any previous pneumococcal vaccination in the past 5 years (includingin a research study)

6. Planned vaccination during the study

7. Allergy:

8. Have an allergy to penicillin or amoxicillin (for main study cohort only)

9. History of a bleeding disorder (e.g., Factor deficiency, coagulopathy, orplatelet disorder), or prior history of significant bleeding or bruisingfollowing IM injections or venepuncture

10. Have previous anaphylaxis or severe adverse reaction to any component/excipientof the vaccine or to any vaccine

11. Allergy to Lidocaine local anaesthetic (for nasal biopsy cohort only)

12. Health History (self-reported or confirmed from GP questionnaire or medicalrecords/summary if deemed necessary): moderate ill health including but not limitedto:

13. Asplenia or dysfuction of the spleen

14. Chronic respiratory disease (e.g. asthma [on medication], COPD, emphysema,bronchiectasis)

15. Chronic heart disease (e.g. angina, ischaemic heart disease, chronic heartfailure) [controlled stable hypertension +/- angina may be included].

16. Chronic kidney disease (e.g. nephrotic syndrome, kidney transplant, ondialysis)

17. Chronic liver disease (e.g. cirrhosis, biliary atresia, hepatitis)

18. Chronic neurological conditions

19. Connective tissue disease

20. Dementia

21. Diabetes mellitus (including diet controlled)

22. Immunosuppression or history of receiving immunosuppressive therapy - at thediscretion of the investigator

23. Individuals with cochlear implants

24. Individuals with major cerebrospinal fluid leaks (e.g. following trauma, majorskull surgery, or requiring CSF shunt)

25. Recurrent otitis media.

26. History of significant unexplained bleeding after a surgical or dentalprocedure (for nasal biopsy participants only)

27. Have any uncontrolled medical/surgical/mental health conditions at thediscretion of the study doctor.

28. Major pneumococcal illness requiring hospitalisation within the last 10 years.

29. Significant mental health condition (e.g previous admissions in a psychiatricunit, at the discretion of the clinician) that would impair the participant'sability to participate in the study

30. Taking Medications:

31. Any medication that may affect the immune system in the last 3 months (e.g.systemic steroids [IM/IV], Roaccutane, disease modifying anti-rheumatoid drugs)

32. Long-term use of antibiotics (see also section of Temporary Exclusion Criteria)

33. Use of any medication or other product (prescription or over-the-counter) forsymptoms of rhinitis or nasal congestion within the last 1 month

34. Use of any medication affecting blood clotting (any oral/injectableanticoagulants)

35. Female participants who are pregnant, lactating or intending on becoming pregnantduring the study

36. Direct caring role or close contact with individuals at higher risk of infection (for main study cohort only):

37. Children under 5 years of age

38. Chronic ill health or immunosuppressed adults

39. Older adults

40. Smoker:

41. Current or ex-smoker (regular cigarettes/cigars/e-cigarette/vaping/smoking ofrecreational drugs) in the last 6 months

42. Previous significant smoking history (more than 20 cigarettes per day for 20years or the equivalent [>20 pack years])

43. Suspected or known current alcohol or drug abuse, as per investigators discretion

44. Overseas travel during the follow-up period (from the time point of inoculation toantibiotic treatment or completion of the 28 day follow up period post inoculation)

45. Any other issue which, in the opinion of the study staff, may:

46. Put the participant or their contacts at risk because of participation in thestudy

47. Adversely affect the interpretation of the study results, or

48. Impair the participant's ability to participate in the study

49. Study site staff or a partner or dependent child of study site staff