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NCT Number: NCT05897879

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

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.

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Key information

Conditions

Bordetella Pertussis, Whooping Cough Bacterial Infections Bacterial Infections and Mycoses Bordetella Infections Gram-Negative Bacterial Infections Infections Respiratory Tract Diseases Respiratory Tract Infections Whooping Cough

Age range

Up to 15 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

CHU de Bordeaux, Bordeaux, France

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About this study

The study design is characterized by 4 work packages:

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Nasopharyngeal swab

Biological

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

Biological

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

Primary outcomes

  1. 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 ;

  2. 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. 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.

Secondary outcomes

  1. 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

  2. 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. 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

Study contacts

Contact information is provided by the study sponsor or research team.

Julie Toubiana, MD

CONTACT

[email protected]

+331 45 68 80 05

Sponsors and collaborators

Lead sponsor

Institut Pasteur

Industry

Collaborators

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

Registry information

Acronym: PERT-SEVEREII

Important dates

Study start
2023
Primary completion
2025
Study completion
2026
First posted
Jun 9, 2023
Registry last updated
May 24, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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