Impact of Bacterial Expression and Immune Response in the Severity of Pertussis

Bordetella Pertussis, Whooping Cough Clinical Trial

— PERT-SEVEREII  

Official title:

Impact of Bacterial Expression and Immune Response in the Severity of Pertussis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05897879
• Other study ID #: 2022-093
• Secondary ID: 2023-A00004-41
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 1, 2023
• Est. completion date: July 1, 2026

Study information

• Verified date: May 2023
• Source: Institut Pasteur
• Contact: Julie Toubiana, MD
• Phone: +331 45 68 80 05
• Email: julie.toubiana[@]pasteur.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 210
• Est. completion date: July 1, 2026
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 15 Years

Eligibility

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.

Related Conditions & MeSH terms

• Bordetella Pertussis, Whooping Cough
• Whooping Cough

Intervention

Biological:
• Nasopharyngeal swab
For hospitalized patients : Nasopharyngeal swab (1 aspiration or 2 swabs (1 in each nostril)) For ambulatory patients : Deep nasal swab: 2 swabs (1 in each nostril), or 1 swab only for children for whom taking 2 swabs is complicated.
• Blood samples
For hospitalized patients : 3 to 7.5 ml For ambulatory patients: Fingertip blood sampling

Locations

Country	Name	City	State
France	CHU de Bordeaux	Bordeaux
France	Hôpital Louis Mourier	Colombes
France	Centre hospitalier intercommunal de Créteil	Créteil
France	Hôpital Roger Salengo	Lille
France	Hospices Civils de Lyon	Lyon
France	Hôpital de la Timone Enfants, APHM	Marseille
France	Hôpital Nord, APHM	Marseille
France	CHU de Nantes	Nantes
France	CHU Armand Trousseau	Paris
France	Hopital Necker	Paris
France	Hôpital Robert Debré	Paris
France	CHU Rouen	Rouen
France	Réseau ACTIV	Saint-Maur-des-Fossés
France	CHU de Toulouse	Toulouse

Sponsors (15)

Lead Sponsor	Collaborator
Institut Pasteur	Centre Hospitalier Intercommunal Creteil, CHR - Hôpital Roger Salengo, CHU de Nantes, Hôpital Armand Trousseau, Hôpital de la Timone, Hôpital Louis Mourier, Hôpital Necker-Enfants Malades, Hôpital Nord - APHM, Hopital Universitaire Robert-Debre, Hospices Civils de Lyon, Réseau ACTIV, University Hospital, Bordeaux, University Hospital, Rouen, University Hospital, Toulouse

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measurement of expression level of Bp genes during infection by Nanostring transcriptomic analysis of Bp isolates from the nasopharynx of children with pertussis.	To identify in a standardized way the microbial "in situ" expression profiles of currently circulating Bp genes during infection in children ;	3 years
Primary	Measurement of plasma cytokine and chemokine concentrations by SIMOA digital ELISA	To determine systemic and respiratory immune responses in children during pertussis.	3 years
Primary	Phenotyping of immune cells by cytometry with a 20-color flow cytometry panel	To determine systemic and respiratory immune responses in children during pertussis.	3 years
Secondary	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	List of microbial genes which expression is modified by recent genomic developments related to vaccine pressure	3 years
Secondary	Measurement of high expression level of Bp genes in all clinical forms of pertussis by Nanostring transcriptomic analysis of Bp isolates	To identify new candidate Bp genes for a future protein vaccine	3 years
Secondary	Measurement of expression level of Bp genes which is associated with severe pertussis by Nanostring transcriptomic analysis of Bp isolates	List of virulence genes differentially expressed during severe pertussis	3 years