Be Part of Research - Trial Details - RATIONALE-15: Carriage to assess the protection of new pneumococcal vaccines- PCV15

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Streptococcus pneumoniae (pneumococcus) causes around 3.7 million infections every year. You can find pneumococcus as part of the nose microflora of healthy adults and children. This harmless state is called “carriage”. Carriage is important because from the nose the bacteria can transmit to others that are susceptible causing life-threatening disease.
Pneumococcus is surrounded by a sugar capsule that is variable and classifies pneumococcus into distinct serotypes. Approved vaccines contain those sugar capsules and protect against the most common disease-causing serotypes. A vaccine called PCV13 has been effective globally because it controls carriage and protects against diseases. Vaccines giving protection against more disease-causing serotypes are becoming available worldwide. PCV15 is like PCV13 but contains two other serotypes, offering wider protection. The aim of this study is to determine if PCV15 protects against carriage.

Healthy adults aged 18-50 years

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Current key exclusion criteria as of 30/07/2025:1. Research Participants:1.1. Participation in another research study, in which procedures performed could compromise the integrity of this study (such as significant volumes of blood taken), or are planning to do so within the trial period1.2. Currently a participant in a previous EHPC trial within the last 2 years 2. Vaccination (self-reported or confirmed from GP questionnaire or medical records/summary if deemed necessary at clinician discretion):2.1. Have had any previous pneumococcal vaccination in the past 5 years (including in a research study)2.2. Planned vaccination during the study3. Allergy:3.1. Have an allergy to penicillin or amoxicillin (for main study cohort only)3.2. History of a bleeding disorder (e.g., Factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture3.3. Have previous anaphylaxis or severe adverse reaction to any component/excipient of the vaccine or to any vaccine3.4. Allergy to Lidocaine local anaesthetic (for nasal biopsy cohort only)4. Health History (self-reported or confirmed from GP questionnaire or medical records/summary if deemed necessary): moderate ill health including but not limited to:4.1. Asplenia or dysfunction of the spleen4.2. Chronic respiratory disease (e.g. asthma [on medication], COPD, emphysema, bronchiectasis)4.3. Chronic heart disease (e.g. angina, ischaemic heart disease, chronic heart failure) [controlled stable hypertension +/- angina may be included]4.4. Chronic kidney disease (e.g. nephrotic syndrome, kidney transplant, on dialysis)4.5. Chronic liver disease (e.g. cirrhosis, biliary atresia, hepatitis)4.6. Chronic neurological conditions4.7. Connective tissue disease4.8. Dementia4.9. Diabetes mellitus (including diet controlled)4.10. Immunosuppression or history of receiving immunosuppressive therapy – at the discretion of the investigator4.11. Individuals with cochlear implants4.12. Individuals with major cerebrospinal fluid leaks (e.g. following trauma, major skull surgery, or requiring CSF shunt)4.13. Recurrent otitis media4.14. History of significant unexplained bleeding after a surgical or dental procedure (for nasal biopsy participants only)4.15. Have any uncontrolled medical/surgical/mental health conditions at the discretion of the study doctor4.16. Major pneumococcal illness requiring hospitalisation within the last 10 years4.17. Significant mental health problems (uncontrolled condition or previous admissions in a psychiatric unit, at the discretion of the clinician) that would impair the participant’s ability to participate in the study5. Taking Medications:5.1. 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)5.2. Long-term use of antibiotics (see also section of Temporary Exclusion Criteria)5.3. Use of nasal steroids from 1 month prior to screening date until visit 8 (day 56)5.4. Use of any medication affecting blood clotting (any oral/injectable anticoagulants)6. Female participants who are pregnant, lactating or intending on becoming pregnant during the study7. Direct caring role or close contact with individuals at higher risk of infection (for main study cohort only):7.1. Children under 5 years of age7.2. Chronic ill health or immunosuppressed adults7.3. Older adults8. Smoker:8.1. Current or ex-smoker (regular cigarettes/cigars/e-cigarette/vaping/smoking of recreational drugs) in the last 6 months8.2. Previous significant smoking history (more than 20 cigarettes per day for 20 years or the equivalent [>20 pack years])9. Suspected or known current alcohol or drug abuse, as per investigator's discretion10. Overseas travel during the follow-up period (from the time point of inoculation to antibiotic treatment or completion of the 23-day follow-up period post inoculation)11. Any other issue which, in the opinion of the study staff, may:11.1. Put the participant or their contacts at risk because of participation in the study11.2. Adversely affect the interpretation of the study results, or11.3. Impair the participant’s ability to participate in the study12. Study site staff or a partner or dependent child of study site staff

Previous key exclusion criteria:1. Research Participants:1.1. Participation in another research study, in which procedures performed could compromise the integrity of this study (such as significant volumes of blood taken), or are planning to do so within the trial period1.2. Currently a participant in a previous EHPC trial within the last 2 years or at the discretion of the study team2. Vaccination (self-reported or confirmed from GP questionnaire or medical records/summary if deemed necessary at clinician discretion):2.1. Have had any previous pneumococcal vaccination in the past 5 years (including in a research study)2.2. Planned vaccination during the study3. Allergy:3.1. Have an allergy to penicillin or amoxicillin (for main study cohort only)3.2. History of a bleeding disorder (e.g., Factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture3.3. Have previous anaphylaxis or severe adverse reaction to any component/excipient of the vaccine or to any vaccine3.4. Allergy to Lidocaine local anaesthetic (for nasal biopsy cohort only)4. Health History (self-reported or confirmed from GP questionnaire or medical records/summary if deemed necessary): moderate ill health including but not limited to:4.1. Asplenia or dysfunction of the spleen4.2. Chronic respiratory disease (e.g. asthma [on medication], COPD, emphysema, bronchiectasis)4.3. Chronic heart disease (e.g. angina, ischaemic heart disease, chronic heart failure) [controlled stable hypertension +/- angina may be included]4.4. Chronic kidney disease (e.g. nephrotic syndrome, kidney transplant, on dialysis)4.5. Chronic liver disease (e.g. cirrhosis, biliary atresia, hepatitis)4.6. Chronic neurological conditions4.7. Connective tissue disease4.8. Dementia4.9. Diabetes mellitus (including diet controlled)4.10. Immunosuppression or history of receiving immunosuppressive therapy – at the discretion of the investigator4.11. Individuals with cochlear implants4.12. Individuals with major cerebrospinal fluid leaks (e.g. following trauma, major skull surgery, or requiring CSF shunt)4.13. Recurrent otitis media4.14. History of significant unexplained bleeding after a surgical or dental procedure (for nasal biopsy participants only)4.15. Have any uncontrolled medical/surgical/mental health conditions at the discretion of the study doctor4.16. Major pneumococcal illness requiring hospitalisation within the last 10 years4.17. Significant mental health problems (uncontrolled condition or previous admissions in a psychiatric unit, at the discretion of the clinician) that would impair the participant’s ability to participate in the study5. Taking Medications:5.1. 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)5.2. Long-term use of antibiotics (see also section of Temporary Exclusion Criteria)5.3. Use of any medication or other product (prescription or over-the-counter) for symptoms of rhinitis or nasal congestion within the last 1 month5.4. Use of any medication affecting blood clotting (any oral/injectable anticoagulants [except aspirin])6. Female participants who are pregnant, lactating or intending on becoming pregnant during the study7. Direct caring role or close contact with individuals at higher risk of infection (for main study cohort only):7.1. Children under 5 years of age7.2. Chronic ill health or immunosuppressed adults7.3. Older adults8. Smoker:8.1. Current or ex-smoker (regular cigarettes/cigars/e-cigarette/vaping/smoking of recreational drugs) in the last 6 months8.2. Previous significant smoking history (more than 20 cigarettes per day for 20 years or the equivalent [>20 pack years])9. Suspected or known current alcohol or drug abuse, as per investigator's discretion10. Overseas travel during the follow-up period (from the time point of inoculation to antibiotic treatment or completion of the 23-day follow-up period post inoculation)11. Any other issue which, in the opinion of the study staff, may:11.1. Put the participant or their contacts at risk because of participation in the study11.2. Adversely affect the interpretation of the study results, or11.3. Impair the participant’s ability to participate in the study12. Study site staff or a partner or dependent child of study site staff

The information gained will help us understand how PCV15 protects people against pneumococcus, meaning that we will be able to improve both this vaccine and future pneumococcal vaccines to protect many lives around the world.
Pneumococcus is responsible for infections including otitis media (OM), sinusitis, pneumonia, bacteraemia and meningitis. Due to inoculating participants with pneumococcus, there is a very low risk of OM, sinusitis, pneumonia, bacteraemia and meningitis. While the risk to individuals of developing any infection is very low, the study is designed to ensure that any risk of invasive disease is minimal (strict inclusion/exclusion criteria, strict safety follow-up, pneumococcal strain that is sensitive to antibiotics and healthy young adult study cohort).
This study can be safely run based on the following experience and provisions. The research team has 14 years of experience in human challenge studies, following very similar protocols and facing similar risks as previous studies. The selected pneumococcal serotype (SPN3) is fully antibiotic sensitive and has been safety tested in 60 healthy participants without safety concerns. Participant selection and exclusion criteria reduce the excess risk of invasive pneumococcal disease associated with comorbid conditions. Participant education regarding the risks of study participation, provision of a safety information leaflet, and close interaction with the study staff. Rigorous and frequent monitoring of the development of symptoms and body temperature. Provision of standby antibiotics to reduce time to treatment, if it is required. 24-hour emergency telephone contact with researchers (including individual daily monitoring for the first 7 days following inoculation) will facilitate access to hospital and/or prompt treatment if required. Within the safety information sheet, participants will be warned to look out for specific symptoms relating to infections caused by Streptococcus pneumoniae.
The researchers now have experience of inoculating and following over 2000 participants using several serotypes, in different adult cohorts and at a range of doses with participants being experimentally colonised, naturally colonised and not colonised during our studies.
In the event that symptoms occur during the inoculation follow-up period, participants will contact the team on the day that the symptoms are noted. The clinical team will assess the participant and use a pre-defined to determine if antibiotics should be commenced, irrespective of the colonisation status at that point. Participants may be reviewed in the study clinic or asked to attend an NHS healthcare treatment facility directly at the investigator's discretion.
The most commonly reported solicited adverse reactions in adults 18 to 49 years of age described in the PCV15 Summary of Product Characteristics (SmPC) were: injection-site pain, fatigue, myalgia, headache, injection-site swelling, injection-site erythema, and arthralgia. The majority of solicited adverse reactions were mild (based on intensity or size) and of short duration (≤3 days); severe reactions (defined as an event that prevents normal daily activity or size of injection site reaction >10 cm) occurred in ≤1.5% of adults across the clinical program. There are no risks of developing pneumococcal pneumonia attributable to a serotype(s) in PCV15 (i.e. given the modification of the infective organism and according susceptibility of that organism to antibiotics).
The majority of sampling methods utilised are not invasive and have no associated risks. The following have the potential for mild, self-limiting risks. Venepuncture may cause slight pain, bruising, light-headedness or fainting. The amount of blood collected during the study will be within the NHS Blood and Transplant guidelines for blood donation. Collection of nasal cells taken during the trial may cause discomfort, eye watering or minor local bleeding. Collection of throat swabs may cause slight discomfort and may elicit a gag reflex. Collection of nasal Wash: participants may swallow saline which may taste salty. Collection of nasopharyngeal/nasal swab: this may cause some discomfort, eye watering or a minor local bleeding. Participants may have mild nasal discomfort or rhinorrhoea following the procedure, which typically settles within 48 hours. Rarely, subjects undergoing nasal biopsy may have an adverse reaction to the local anaesthetic used. The risk of local bleeding which may require further outpatient ENT intervention such as nasal packing or cautery is <1%. Rarely, subjects may need to be admitted for observation to an ENT acute ward for management of bleeding. Surgical intervention to manage epistaxis in the operating theatre following this procedure is extremely rare. All participants who undergo a nasal biopsy will receive a safety telephone review at 24 hours post-procedure and will have 24/7 access to a study doctor for up to 3 weeks post-procedure.

RATIONALE-15: Carriage to assess the protection of new pneumococcal vaccines- PCV15

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RATIONALE-15: Carriage to assess the protection of new pneumococcal vaccines- PCV15

Not Recruiting

Open to: All Genders

Age: Adult

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