Campylobacter jejuni strain CG8421: A refined model for the study of campylobacteriosis and evaluation of campylobacter vaccines in human subjects

David R. Tribble, Shahida Baqar, Marya P. Carmolli, Chad Porter, Kristen K. Pierce, Katrin Sadigh, Patricia Guerry, Catherine J. Larsson, David Rockabrand, Cassandra H. Ventone, Frederic Poly, Caroline E. Lyon, Sandra Dakdouk, Ann Fingar, Theron Gilliland, Patrick Daunais, Erika Jones, Stacia Rymarchyk, Christopher Huston, Michael DarsleyBeth D. Kirkpatrick

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Background: A robust human challenge model for Campylobacter jejuni is an important tool for the evaluation of candidate vaccines. The previously established model conveys a potential risk of Guillain-Barre syndrome attributable to lipooligosaccharide ganglioside mimicry. This work establishes a new C. jejuni human challenge model that uses a strain (CG8421) without ganglioside mimicry and that applies Campylobacter-specific cellular immunity screening to achieve high attack rates at lower inoculum doses. Methods: Healthy Campylobacter-naive adults participated in an open-label challenge trial. Participants were dosed with C. jejuni CG8421 and followed as inpatients. Pattern of illness, bacterial shedding, and immunologic responses were determined. Results: Following screening, 23 subjects received 1×10 6 or 1×10 5 colony-forming units of C. jejuni, with attack rates (percentage of patients who became ill) of 100% (1×10 6 colony-forming units) or 93% (1×10 5 colony-forming units). Every subject shed CG8421; the median time to diarrhea onset was 72.3 h (interquartile range, 53.9-99.9 h). Symptoms included abdominal cramps (74%), nausea (65%), and fever (39%). No major safety concerns occurred, including bacteremia, hypotension, or postinfectious sequelae. Unexpectedly, recrudescent infection occurred in 2 subjects (1 subject without Campylobacter-specific adaptive immune responses and 1 with azithromycin resistance acquired in vivo); both infections cleared after receipt of additional antibiotics. Cumulative Campylobacter-specific immune responses were as follows: serologic response occurred in 87% (immunoglobulin [Ig] A) and 48% (IgG) of subjects, in vitro interferon-γ production occurred in 91% of subjects, and 96% of subjects had IgA antibody-secreting cells and fecal IgA detected. Conclusions: The C. jejuni CG8421 challenge model provides a safe and effective tool, without the risk of Guillain-Barré syndrome. The model demonstrates high attack rates after lower doses of challenge inoculum, provides further understanding of immunologic responses, and permits future investigation of candidate Campylobacter vaccines.

Original languageEnglish
Pages (from-to)1512-1519
Number of pages8
JournalClinical Infectious Diseases
Volume49
Issue number10
DOIs
StatePublished - Nov 2009
Externally publishedYes

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