The overall goal of this study is to establish a PRN-deficient pertussis Controlled Human Infection Model (CHIM) that represents currently circulating isolates, in the context of a North American exposure (vaccination and infection) pedigree.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
60
Intranasal inoculation of Bordetella pertussis J820 in each naris on Day 1 of the study.
Canadian Center for Vaccinology
Halifax, Nova Scotia, Canada
RECRUITINGPrimary Outcome Measures
Establish a PRN-deficient pertussis CHIM that identifies the lowest challenge dose that successfully \& safely infects nearly all (≥85%) participants challenged (HID) \& produces the highest achievable rate of symptomatic infection (HSD), including cough, using an adaptive dose response design. This is contingent upon determining each participant's clinical outcome post-challenge to compute the rate of symptomatic infection \& rate of overall infection per dose group, based on outcomes for all participants receiving that dose. As a derived variable, clinical outcomes will be measured/determined using programmed case definitions previously designed to emulate the natural course of early pertussis disease following experimentally induced pertussis infection. Clinical outcome measures include: 1. B. pertussis lab testing of samples (culture, PCR, serology) 2. Clinical assessments (safety bloods, physical exams, DCs, symptom self-reporting).
Time frame: Study Day 1 up to Study Day 29
Secondary Outcome Measures
• To measure the rate of cough and describe the clinical presentation via: 1. Self-reporting 2. Clinical assessment
Time frame: Study Day 1 up to Study Day 29
Secondary Outcome Measures
• To evaluate the immune response following challenge associated with infection via: 1\. Humoral immune responses (analyte; unit; sample; technique): A) Anti-PT Antibodies; IU/mL; Serum; ELISA B) Anti-FHA Antibodies; IU/mL; Serum; ELISA C) Anti-PRN Antibodies; IU/mL; Serum; ELISA D) Anti-FIM Antibodies; EU/mL; Serum; ELISA
Time frame: Day 1 up to Study Day 181
Secondary Outcome Measure
• To evaluate the immune response following challenge associated with infection via: 2\. Cellular \& Cellular-mediated immune responses Cellular: A) Eotaxin-2, Perfornin, Granzyme-A \& Granzyme-B; all pg/mL, by nasal wash using Luminex Cellular-mediated: A) Neutrophil CD16+, B cell CD19+, T Cell CD4+, T cells CD8+, Mucosal associated invariant T cell(MAIT) cells, NK cell CD3-CD56+, Monocyte CD14+, Eosinophil Siglec8+, gamma delta T cell; all % \& absolute count, by whole blood \& nasal swab using Flow cytometry
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Time frame: Time Frame: Day 1 up to Study Day 181
Secondary Outcome Measures
• To explore the time course of azithromycin therapy in clearing infection and/or symptoms, via testing during treatment as applicable via: 1\. B. pertussis laboratory testing of samples (culture, PCR): A) The mean number of days to culture negativity (i.e., bacterial count of zero in both NW and NPA samples) in days (with a 95% confidence interval) following treatment. B) The mean number of days to PCR negativity (i.e., PCR negative for each of the targets, that is IS481 and ptxS1 in both NW and NPA samples in days (with a 95% CI) following treatment. C) The cumulative proportion of participants that are negative by day following treatment by culture and PCR.
Time frame: Study Day 1 up to Study Day 29
Secondary Outcome Measure
• To explore the time course of azithromycin therapy in clearing infection and/or symptoms, via testing during treatment as applicable via: 2\. Clinical assessments (as needed): A) The mean number of days to symptom resolution (i.e., no reporting/detection of symptoms and/or signs) in days (with a 95% confidence interval) following treatment. B) The cumulative proportion of participants with resolved pertussis symptoms by day following treatment.
Time frame: Time Frame: Study Day 1 up to Study Day 29