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

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.

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

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.