Pertussis CHIM Biorepository

Key points

  • Scientists recently developed a pertussis controlled human infection model (pertussis CHIM).
  • The aim was to build a foundation for and accelerate development and licensure of next-generation pertussis vaccines in the United States.
  • Biological samples from this pertussis CHIM are available for researchers.
  • Request samples by following the application process.
An image of Bordetella pertussis that was generated by a computer based on scanning electron microscopic imagery.

Overview

The first North American pertussis CHIM study began enrolling participants in July 2022. The objective of this study was to establish a pertussis CHIM. Researchers aimed to identify a Bordetella pertussis challenge dose that could safely and reproducibly achieve mild, symptomatic infection in healthy adults aged 18–40 years. The B. pertussis strain (D420) used in this study was a well-characterized strain obtained from a U.S. infant with pertussis. The Canadian Center for Vaccinology, located in Halifax, Canada, established the CDC-supported North American pertussis CHIM platform.

Furthering research

Biological samples obtained from all CDC-funded studies using the pertussis CHIM platform are stored in a central biorepository (CBR) at CDC. CDC can share these specimens with the wider scientific community in North America to facilitate collaboration on pertussis research.

The pertussis CHIM specimens in the CBR are under the custodianship of CDC's Meningitis, Pertussis, and Diphtheria Laboratory Branch, who is responsible for reviewing and approving requests.

Keep Reading CHIM Biorepository Application Process

Participants

Participants included people aged 18–40 years who received whole-cell or acellular pertussis vaccines for their primary vaccination series. People who consented to participate and who passed an received a challenge dose of the clinically characterized pertactin-producing B. pertussis strain D420 administered intranasally.

Challenged participants remained in an isolation room at the Canadian Center for Vaccinology Challenge Unit for 16–21 days or until they developed mild symptoms. All challenged participants received azithromycin as rescue and/or eradication therapy prior to leaving the unit and were followed for one year.

Biological samples

Researchers collected biological samples at multiple time points during the inpatient stay as well as on follow-up visits. Biological samples included:

  • Nasal washes
  • Nasopharyngeal aspirates
  • Peripheral blood mononuclear cells (PBMCs)
  • Plasma
  • Saliva
  • Serum
  • Whole blood

Study phases

Dose escalation phase

The study included a dose escalation phase to identify a dose that achieved mild, symptomatic infection in 70%–90% of participants. Six cohorts were enrolled in the dose escalation phase until the human infective dose (HID70-90) was reached.

Dose confirmation phase

The dose escalation phase was followed by the dose confirmation phase to confirm the infectious endpoint. This phase included one cohort of 10 participants who received the HID70-90 dose. Additional cohorts received doses that were lower (half-log) and higher (half- and full log) than the HID70-90.

A majority of participants completed the inpatient portion of the study.

Sub-study

A sub-study was added to strengthen and complement the trial's primary goal of developing a safe model of B. pertussis infection in healthy adults. Specifically, an additional cohort of 10 participants received a new higher dose to explore whether

  • A full log dose above HID70-90 consistently induces cough
  • The pertussis CHIM model can be titrated to induce multiple models:
    • Colonization only
    • Colonization with respiratory symptoms without cough
    • Respiratory symptoms with cough
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Content Source:
National Center for Immunization and Respiratory Diseases; Division of Bacterial Diseases