Clinical trial NCT05897879: Impact of Bacterial Expression and Immune Response in the Severity of Pertussis
Official title: Impact of Bacterial Expression and Immune Response in the Severity of Pertussis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Bordetella Pertussis, Whooping Cough
Keywords: vaccination
Lead sponsor: Institut Pasteur
Sponsor class: INDUSTRY
Collaborators: name: Hôpital Necker-Enfants Malades
name: Hospices Civils de Lyon
name: Hopital Universitaire Robert-Debre
name: Centre Hospitalier Intercommunal Creteil
name: Nantes University Hospital
name: Réseau ACTIV
name: Hôpital Armand Trousseau
name: CHR - Hôpital Roger Salengo
name: Hôpital Nord - APHM
name: Hôpital Louis Mourier
name: University Hospital, Toulouse
name: University Hospital, Bordeaux
name: Hôpital de la Timone
name: University Hospital, Rouen
First posted: 2023-06-09
Enrollment: 210
Sex: ALL
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The resurgence of pertussis is associated with an evolutionary mechanism under the pressure of current acellular vaccines, with a possible impact on vaccine effectiveness and disease expression. Little is known about the mechanisms involved in the clinical variability of pertussis, including its most severe malignant form observed in infants (mortality between 50-80%). The main challenges are: (i) the lack of knowledge about the gene expression of B. pertussis strains currently circulating during human infection, incorporating evolutionary changes and vaccine-induced selective pressure; (ii) the poor understanding of the variability in clinical expression of pertussis, and (iii) the lack of biomarkers to predict disease severity or prognosis in infants.

An integrative strategy combining a clinical, microbiological, immunological and 'omic' approach from a prospective cohort of children with pertussis will be used to identify

1. 'in situ' expression profiles of B. pertussis genes and proteins incorporating recent evolutionary changes and
2. a systemic and respiratory immune signature in B. pertussis-infected children according to severity.

Results should furthermore serve as a prerequisite for the identification of severity biomarkers and new vaccine antigen candidates taking into account specific immune responses in infants.

Detailed description: The study design is characterized by 4 work packages:

1. Collection of clinical data and biological samples (deep nasal swab, blood sample) from children with pertussis
2. Construction and validation of a microbial panel of 200 genes of interest (involved in virulence and/or potential vaccine antigens) for transcriptomic analysis
3. Transcriptomic study using the panel of interest of B. pertussis isolates from nasopharyngeal swabs preserved with an RNA stabilizer, using the Nanostring® technique
4. Study of the immune response during pertussis

Eligibility criteria: Inclusion Criteria:

* be between the ages of 0 and 15 years inclusive
* be suspected of having pertussis by the physician in charge, with the prescription of a diagnostic PCR (pertussis PCR, which may be a syndromic PCR, a PCR targeting IS481 and/or IS1001)
* be free of any pathology/treatment that may influence the immune response (autoimmune/inflammatory pathology or immune deficiency not listed above, hepatic insufficiency, taking immunosuppressive treatment (including taking oral corticosteroids with a dose ≥ 10 mg/d Prednisone equivalent for more than 15 days)
* Have received age-appropriate information and written assent or consent from their parents/legal guardians
* be affiliated with or benefiting from a social security plan

Exclusion Criteria:

* Patient with any pathology/treatment that may influence the immune response (autoimmune/inflammatory pathology or immune deficiency not listed above, hepatic failure, taking immunosuppressive therapy (including oral corticosteroids with dose ≥ 10 mg/d prednisone equivalent for more than 15 days)
* Use of antibiotics active against pertussis in the 24 hours preceding the sampling
* Delay between the result of the diagnostic sample (pertussis PCR) and the day of inclusion \> 48 hours
* Patient's condition that, in the opinion of the physician, is incompatible with the expanded/additional sampling(s) required by the study
* Infant with a weight \< 2.5 kg at the time of inclusion.

Primary outcomes:
measure: Measurement of expression level of Bp genes during infection by Nanostring transcriptomic analysis of Bp isolates from the nasopharynx of children with pertussis.
timeFrame: 3 years
measure: Measurement of plasma cytokine and chemokine concentrations by SIMOA digital ELISA
timeFrame: 3 years
measure: Phenotyping of immune cells by cytometry with a 20-color flow cytometry panel
timeFrame: 3 years
Secondary outcomes:
measure: Measurement of expression level of Bp genes which is modified by recent gene developments related to vaccine pressure by Nanostring transcriptomic analysis of Bp isolates
timeFrame: 3 years
measure: Measurement of high expression level of Bp genes in all clinical forms of pertussis by Nanostring transcriptomic analysis of Bp isolates
timeFrame: 3 years
measure: Measurement of expression level of Bp genes which is associated with severe pertussis by Nanostring transcriptomic analysis of Bp isolates
timeFrame: 3 years
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Colombes
country: France
facility: Hôpital Louis Mourier
city: Créteil
country: France
facility: Centre hospitalier intercommunal de Créteil
city: Lille
country: France
facility: Hôpital Roger Salengo
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Marseille
country: France
facility: Hôpital de la Timone Enfants, APHM
city: Marseille
country: France
facility: Hôpital Nord, APHM
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: CHU Armand Trousseau
city: Paris
country: France
facility: Hopital Necker
city: Paris
country: France
facility: Hôpital Robert Debré
city: Rouen
country: France
facility: CHU Rouen
city: Saint-Maur-des-Fossés
country: France
facility: Réseau ACTIV
city: Toulouse
country: France
facility: CHU de Toulouse
Study officials:
affiliation: Institut Pasteur
name: Julie Toubiana, MD
role: STUDY_DIRECTOR
References: