Impact of Bacterial Expression and Immune Response in the Severity of Pertussis (PERT-SEVEREII)

June 1, 2023 updated by: Institut Pasteur

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Estimated)

210

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Bordeaux, France
        • CHU de Bordeaux
        • Contact:
          • Emilie Pauquet, MD
      • Colombes, France
        • Hôpital Louis Mourier
        • Contact:
          • Romain Basmaci, MD
      • Créteil, France
        • Centre Hospitalier Intercommunal de Créteil
        • Contact:
          • Fouad Madhi, MD
      • Lille, France
        • Hôpital Roger Salengo
        • Contact:
          • François DUBOS, MD
      • Lyon, France
        • Hospices Civils de Lyon
        • Contact:
          • Antoine Ouziel, MD
      • Marseille, France
        • Hôpital de la Timone Enfants, APHM
        • Contact:
          • Aurélie Morand, MD
      • Marseille, France
        • Hôpital Nord, APHM
        • Contact:
          • Philippe Minodier, MD
      • Nantes, France
        • CHU de Nantes
        • Contact:
          • David Malorey, MD
      • Paris, France
        • Hôpital Robert Debré
        • Contact:
          • Albert Faye, MD
      • Paris, France
        • Hopital Necker
        • Contact:
          • Julie Toubiana, MD
      • Paris, France
        • CHU Armand Trousseau
        • Contact:
          • Mathie Lorrot, MD
      • Rouen, France
        • CHU Rouen
        • Contact:
          • Didier Pinquier, MD
      • Saint-Maur-des-Fossés, France
        • Réseau ACTIV
        • Contact:
          • Robert COHEN, MD
      • Toulouse, France
        • CHU de Toulouse
        • Contact:
          • Camille BREHIN, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Children between 0 and 15 years with suspected pertussis
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.

Biological: Blood samples
For hospitalized patients : 3 to 7.5 ml For ambulatory patients: Fingertip blood sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measurement of expression level of Bp genes during infection by Nanostring transcriptomic analysis of Bp isolates from the nasopharynx of children with pertussis.
Time Frame: 3 years
To identify in a standardized way the microbial "in situ" expression profiles of currently circulating Bp genes during infection in children ;
3 years
Measurement of plasma cytokine and chemokine concentrations by SIMOA digital ELISA
Time Frame: 3 years
To determine systemic and respiratory immune responses in children during pertussis.
3 years
Phenotyping of immune cells by cytometry with a 20-color flow cytometry panel
Time Frame: 3 years
To determine systemic and respiratory immune responses in children during pertussis.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 3 years
List of microbial genes which expression is modified by recent genomic developments related to vaccine pressure
3 years
Measurement of high expression level of Bp genes in all clinical forms of pertussis by Nanostring transcriptomic analysis of Bp isolates
Time Frame: 3 years
To identify new candidate Bp genes for a future protein vaccine
3 years
Measurement of expression level of Bp genes which is associated with severe pertussis by Nanostring transcriptomic analysis of Bp isolates
Time Frame: 3 years
List of virulence genes differentially expressed during severe pertussis
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Pasteur

Collaborators

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

Investigators

  • Study Director: Julie Toubiana, MD, Institut Pasteur

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2023

Primary Completion (Estimated)

July 1, 2025

Study Completion (Estimated)

July 1, 2026

Study Registration Dates

First Submitted

May 22, 2023

First Submitted That Met QC Criteria

June 1, 2023

First Posted (Actual)

June 9, 2023

Study Record Updates

Last Update Posted (Actual)

June 9, 2023

Last Update Submitted That Met QC Criteria

June 1, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-093
  • 2023-A00004-41 (Other Identifier: ID RCB)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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