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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
91
Dose-ranging and reproducibility study of SPN3 inoculation AND targeted booster inoculation at day-14, where prime inoculation fails to lead to experimental colonisation
Dose-ranging study of SPN3 inoculation AND targeted booster inoculation at day-14, where prime inoculation fails to lead to experimental colonisation
Liverpool School of Tropical Medicine
Liverpool, United Kingdom
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)
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)
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