CompletedNCT05535868Challenge3Updated Jun 29, 2026Results posted

Experimental Human Pneumococcal Challenge With SPN3

An interventional study of Serotype 3 Experimental Human Pneumococcal Challenge - Liverpool Isolate (LIV014-S3) and Serotype 3 Experimental Human Pneumococcal Challenge - Malawi Isolate (MLW-10V) in Streptococcus Pneumonia and Controlled Human Infection, sponsored by Liverpool School of Tropical Medicine. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-06-29.

Sponsored by Liverpool School of Tropical Medicine · Not applicable, Interventional, and Prevention

Phase: Not applicable
Study type: Interventional
Enrollment: 91
Allocation: Non-randomized
Ages: 18 Years to 50 Years
Sex: All

Study summary

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.

Read the detailed description

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.

Conditions studied

Streptococcus Pneumonia
Controlled Human Infection

Browse trials for

Pneumonia 2,044

Keywords

streptococcus pneumoniae
pneumococcus
controlled human infection
serotype 3
SPN3
Adult
Healthy volunteers

In context

Pneumonia

2,044 studies on the registry are indexed under Pneumonia; 283 are open to participants now.

This study's enrollment of 91 is below the median of 106 across 1,247 interventional studies indexed under Pneumonia.

Browse Pneumonia studies →

Lead sponsor

Liverpool School of Tropical Medicine is the lead sponsor of 57 studies on the registry; 24 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 50 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Eligibility criteria

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

Study design

Phase: Not applicable
Primary purpose: Prevention
Allocation: Non-randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 91 participants (actual)

Study arms

Experimental
MLW-10V, 10000 CFU/ml
Malawi isolate, low dose
Other: Serotype 3 Experimental Human Pneumococcal Challenge - Malawi Isolate (MLW-10V)
Experimental
MLW-10V, 20000 CFU/ml
Malawi isolate, intermediate dose
Other: Serotype 3 Experimental Human Pneumococcal Challenge - Malawi Isolate (MLW-10V)
Experimental
MLW-10V, 80000 CFU/ml
Malawi isolate, higher dose
Other: Serotype 3 Experimental Human Pneumococcal Challenge - Malawi Isolate (MLW-10V)
Experimental
LIV014-S3, 10000 CFU/ml
Liverpool isolate, low dose
Other: Serotype 3 Experimental Human Pneumococcal Challenge - Liverpool Isolate (LIV014-S3)
Experimental
LIV014-S3, 20000 CFU/ml
Liverpool isolate, intermediate dose
Other: Serotype 3 Experimental Human Pneumococcal Challenge - Liverpool Isolate (LIV014-S3)
Experimental
LIV014-S3, 80000 CFU/ml
Liverpool isolate, higher dose (includes dose-ranging and reproducibility study participants, since the reproducibility study only included this isolate and dose)
Other: Serotype 3 Experimental Human Pneumococcal Challenge - Liverpool Isolate (LIV014-S3)

Interventions

OtherSerotype 3 Experimental Human Pneumococcal Challenge - Liverpool Isolate (LIV014-S3)
Dose-ranging and reproducibility study of SPN3 inoculation AND targeted booster inoculation at day-14, where prime inoculation fails to lead to experimental colonisation
Also known as: EHPC, SPN3 inoculation, LIV014-S3, Targeted booster
OtherSerotype 3 Experimental Human Pneumococcal Challenge - Malawi Isolate (MLW-10V)
Dose-ranging study of SPN3 inoculation AND targeted booster inoculation at day-14, where prime inoculation fails to lead to experimental colonisation
Also known as: EHPC, SPN3 inoculation, MLW-10V, Targeted booster

What researchers measure

Primary outcomes

To Determine the Optimal SPN3 Dose and Isolate to Establish Colonisation of the Nasopharynx in Healthy Adults
The proportion of participants with experimental SPN3 colonisation of the nasopharynx, determined by SPN3 presence in classical microbiological culture in at least one nasal wash (NW) sample, at any time point following one or two inoculations (combined and individually). This will be assessed for each isolate and dose separately.
Time frame: From inoculation (day 0) to the final visit for each participant (28 days post-inoculation)

Secondary outcomes

To Determine the Density of Experimental SPN3 Colonisation of the Nasopharynx.
The bacterial density of experimental SPN3 colonisation of the nasopharynx in NW, at each and any time point following one or two inoculations (combined and individually), determined by classical microbiological culture, assessed for each isolate and dose separately. The number of participants analysed includes only the participants who developed SPN3 colonisation in each arm/group, rather than the total number of participants inoculated.
Time frame: From inoculation (day 0) to the final visit for each participant (28 days post-inoculation)
To Determine the Duration of Experimental SPN3 Colonisation of the Nasopharynx.
The duration of experimental SPN3 colonisation of nasopharynx determined by the last NW sample following one or two inoculations in which SPN3 is detected by classical microbiological culture, assessed for each isolate and dose separately. Note - number of participants analyzed in this outcome measure is different (and lower) than overall number of participants in participant flow section, because duration of colonisation can only apply to participants who developed experimental colonisation from at least one timepoint post-inoculation.
Time frame: From inoculation (day 0) to the final visit for each participant (28 days post-inoculation)

Results

Posted Jun 29, 2026

Limitations and caveats

This study was conducted in a healthy UK volunteer populatio (so potentially less translatable to those with chronic illnesses or of different ages or from different countries), used one serotype and two isolates only. Data collected for a few e-diary symptoms carried a high degree of subjectivity, such as trouble concentrating; these will be reconsidered in future studies.

Participant flow

Participant flow — Overall Study
Milestone	MLW-10V, 10000 CFU/ml	MLW-10V, 20000 CFU/ml	MLW-10V, 80000 CFU/ml	LIV014-S3, 10000 CFU/ml	LIV014-S3, 20000 CFU/ml	LIV014-S3, 80000 CFU/ml
Started	9	10	10	7	10	40
Day 2 post-inoculation	9	10	10	7	10	40
Day 7 post-inoculation	9	10	10	7	10	40
Day 13 post-inoculation	9	10	10	7	10	40
Day 16 post-inoculation	9	10	10	7	10	40
Day 21 post-inoculation	9	10	10	7	10	40
Day 28 post-inoculation	9	10	10	7	10	40
Completed	9	10	10	7	10	40
Not completed	0	0	0	0	0	0

Outcome measures

PrimaryTo Determine the Optimal SPN3 Dose and Isolate to Establish Colonisation of the Nasopharynx in Healthy Adults

The proportion of participants with experimental SPN3 colonisation of the nasopharynx, determined by SPN3 presence in classical microbiological culture in at least one nasal wash (NW) sample, at any time point following one or two inoculations (combined and individually). This will be assessed for each isolate and dose separately.

Time frame:: From inoculation (day 0) to the final visit for each participant (28 days post-inoculation)
Reported as:: Count of participants · Participants

To Determine the Optimal SPN3 Dose and Isolate to Establish Colonisation of the Nasopharynx in Healthy Adults
Participants	MLW-10V, 10000 CFU/ml	MLW-10V, 20000 CFU/ml	MLW-10V, 80000 CFU/ml	LIV014-S3, 10000 CFU/ml	LIV014-S3, 20000 CFU/ml	LIV014-S3, 80000 CFU/ml
Rate of experimental colonisation after prime inoculation — Experimental colonisation following targeted booster inoculation	4	1	6	1	4	28
Rate of experimental colonisation after prime inoculation — Negative for experimental colonisation after targeted booster inoculation	5	9	4	6	6	12
Rate of experimental colonisation after targeted booster — Experimental colonisation following targeted booster inoculation	5	2	8	1	8	34
Rate of experimental colonisation after targeted booster — Negative for experimental colonisation after targeted booster inoculation	4	8	2	6	2	6

SecondaryTo Determine the Density of Experimental SPN3 Colonisation of the Nasopharynx.

The bacterial density of experimental SPN3 colonisation of the nasopharynx in NW, at each and any time point following one or two inoculations (combined and individually), determined by classical microbiological culture, assessed for each isolate and dose separately. The number of participants analysed includes only the participants who developed SPN3 colonisation in each arm/group, rather than the total number of participants inoculated.

Time frame:: From inoculation (day 0) to the final visit for each participant (28 days post-inoculation)
Reported as:: Geometric mean · Colony forming units per millilitre

To Determine the Density of Experimental SPN3 Colonisation of the Nasopharynx.
Colony forming units per millilitre	MLW-10V, 10000 CFU/ml	MLW-10V, 20000 CFU/ml	MLW-10V, 80000 CFU/ml	LIV014-S3, 10000 CFU/ml	LIV014-S3, 20000 CFU/ml	LIV014-S3, 80000 CFU/ml
To Determine the Density of Experimental SPN3 Colonisation of the Nasopharynx.	100 (10 to 1000)	50 (1 to 175)	300 (100 to 1000)	1 (1 to 1)	300 (50 to 10000)	175 (100 to 1000)

SecondaryTo Determine the Duration of Experimental SPN3 Colonisation of the Nasopharynx.

The duration of experimental SPN3 colonisation of nasopharynx determined by the last NW sample following one or two inoculations in which SPN3 is detected by classical microbiological culture, assessed for each isolate and dose separately. Note - number of participants analyzed in this outcome measure is different (and lower) than overall number of participants in participant flow section, because duration of colonisation can only apply to participants who developed experimental colonisation from at least one timepoint post-inoculation.

Time frame:: From inoculation (day 0) to the final visit for each participant (28 days post-inoculation)
Reported as:: Count of participants · Participants

To Determine the Duration of Experimental SPN3 Colonisation of the Nasopharynx.
Participants	MLW-10V, 10000 CFU/ml	MLW-10V, 20000 CFU/ml	MLW-10V, 80000 CFU/ml	LIV014-S3, 20000 CFU/ml	LIV014-S3, 80000 CFU/ml
Participants with ongoing experimental colonisation at day 13 post-prime inoculation	4	0	5	4	19
Participants with ongoing experimental colonisation at day 28 post-prime inoculation	3	0	5	4	19
Participants with ongoing experimental colonisation at day 14 post-targeted booster inoculation	1	1	1	3	6

Adverse events

Collected over For all adverse events, these are from enrolment until end of follow-up, up to 28 days post-inoculation.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
MLW-10V, 10000 CFU/ml	0/9 (0%)	0/9 (0%)	1/9 (11.1%)
MLW-10V, 20000 CFU/ml	0/10 (0%)	0/10 (0%)	9/10 (90%)
MLW-10V, 80000 CFU/ml	0/10 (0%)	0/10 (0%)	5/10 (50%)
LIV014-S3, 10000 CFU/ml	0/7 (0%)	0/7 (0%)	5/7 (71.4%)
LIV014-S3, 20000 CFU/ml	0/10 (0%)	0/10 (0%)	5/10 (50%)
LIV014-S3, 80000 CFU/ml	0/40 (0%)	0/40 (0%)	28/40 (70%)

Most frequent other events

Most frequent other events
Event	MLW-10V, 10000 CFU/ml	MLW-10V, 20000 CFU/ml	MLW-10V, 80000 CFU/ml	LIV014-S3, 10000 CFU/ml	LIV014-S3, 20000 CFU/ml	LIV014-S3, 80000 CFU/ml
Sore throat (pharyngitis)Infections and infestations	1/9	8/10	4/10	4/7	5/10	25/40
HeadacheGeneral disorders	0/9	5/10	1/10	1/7	2/10	19/40
CoughRespiratory, thoracic and mediastinal disorders	0/9	3/10	1/10	2/7	2/10	4/40
FeverInfections and infestations	0/9	2/10	0/10	0/7	0/10	8/40
EaracheEar and labyrinth disorders	0/9	1/10	1/10	0/7	1/10	2/40

Baseline characteristics

Age, sex and race / ethnitcity are reported for each isolate and each dose.

Age, Continuous
Age, Continuous(Years)	MLW-10V, 10000 CFU/ml	MLW-10V, 20000 CFU/ml	MLW-10V, 80000 CFU/ml	LIV014-S3, 10000 CFU/ml	LIV014-S3, 20000 CFU/ml	LIV014-S3, 80000 CFU/ml	Total
Median	28 (21 to 33)	20 (20 to 21)	20 (19 to 21)	28 (26 to 36)	21 (20 to 22)	24 (20 to 28)	22 (20 to 28)

Sex: Female, Male
Sex: Female, Male(Participants)	MLW-10V, 10000 CFU/ml	MLW-10V, 20000 CFU/ml	MLW-10V, 80000 CFU/ml	LIV014-S3, 10000 CFU/ml	LIV014-S3, 20000 CFU/ml	LIV014-S3, 80000 CFU/ml	Total
Female	7	6	8	5	9	22	57
Male	2	4	2	2	1	18	29

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	MLW-10V, 10000 CFU/ml	MLW-10V, 20000 CFU/ml	MLW-10V, 80000 CFU/ml	LIV014-S3, 10000 CFU/ml	LIV014-S3, 20000 CFU/ml	LIV014-S3, 80000 CFU/ml	Total
Asian	0	2	0	0	1	9	12
Black	0	0	1	0	0	1	2
Other	0	1	0	1	3	2	7
White	9	7	9	6	6	28	65

Study locations

1 site

Liverpool School of Tropical Medicine
Liverpool, L7 8XZ, United Kingdom

References and documents

Publications

Hazenberg P, Robinson RE, Farrar M, Solorzano C, Hyder-Wright A, Liatsikos K, Brunning J, Fleet H, Bettam A, Howard A, Kenny-Nyazika T, Urban B, Mitsi E, El Safadi D, Davies K, Lesosky M, Gordon SB, Ferreira DM, Collins AM. Serotype 3 Experimental Human Pneumococcal Challenge (EHPC) study protocol: dose ranging and reproducibility in a healthy volunteer population (challenge 3). BMJ Open. 2024 Jan 10;14(1):e075948. doi: 10.1136/bmjopen-2023-075948. PubMed 38199622 ↗

Study documents

Study protocol · Jun 23, 2023
Statistical analysis plan · Mar 23, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 29, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT05535868
Lead sponsor: Liverpool School of Tropical Medicine
Collaborators: Merck Sharp & Dohme LLC, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Liverpool University Hospitals NHS Foundation Trust, University of Oxford
Responsible party: Sponsor
First posted: Sep 10, 2022
Start date: Aug 1, 2022
Primary completion: Nov 21, 2023
Completion: Nov 21, 2023
Results posted: Jun 29, 2026
Last update: Jun 29, 2026

Study contacts

Andrea Collins, MBChB, PhD

principal investigator · Senior Clinical Lecturer

Oversight

Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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