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

Condition(s) studied

Investigational drug(s) / intervention(s)

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

Study 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.

Eligibility

Primary outcome measure(s)

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

Trial sites (14)

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