Campylobacter jejuni strain CG8421: a refined model for the study of Campylobacteriosis and evaluation of Campylobacter vaccines in human subjects.
Autor(es): Tribble David R,Baqar Shahida,Carmolli Marya P,Porter Chad,Pierce Kristen K,Sadigh Katrin,Guerry Patricia,Larsson Catherine J,Rockabrand David,Ventone Cassandra H,Poly Frederic,Lyon Caroline E,Dakdouk Sandra,Fingar Ann,Gilliland Theron,Daunais Patrick,Jones Erika,Rymarchyk Stacia,Huston Christopher,Darsley Michael,Kirkpatrick Beth D
Resumo: 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-Barré 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. 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. Following screening, 23 subjects received 1 X 10(6) or 1 X 10(5) colony-forming units of C. jejuni, with attack rates (percentage of patients who became ill) of 100% (1 X 10(6) colony-forming units) or 93% (1 X 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-gamma production occurred in 91% of subjects, and 96% of subjects had IgA antibody-secreting cells and fecal IgA detected. 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.
Imprenta: Clinical Infectious Diseases, v. 49, n. 10, p. 1512-1519, 2009
Identificador do objeto digital: 10.1086/644622
Descritores: Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Cytopathology ; Guillain-Barre Syndrome - Immune response ; Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - Antibodies ; Guillain-Barre Syndrome - Cytokines ; Guillain-Barre Syndrome - Immune response ; Guillain-Barre Syndrome - Vaccine ; Guillain-Barre Syndrome - Immunology
Data de publicação: 2009