Campylobacter jejuni strain CG8421: a refined model for the study of Campylobacteriosis and evaluation of Campylobacter vaccines in human subjects.
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-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.


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 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.


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.
Department of Enteric Diseases, Naval Medical Research Center, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
David R
DR
Tribble
Shahida
S
Baqar
Marya P
MP
Carmolli
Chad
C
Porter
Kristen K
KK
Pierce
Katrin
K
Sadigh
Patricia
P
Guerry
Catherine J
CJ
Larsson
David
D
Rockabrand
Cassandra H
CH
Ventone
Frederic
F
Poly
Caroline E
CE
Lyon
Sandra
S
Dakdouk
Ann
A
Fingar
Theron
T
Gilliland
Patrick
P
Daunais
Erika
E
Jones
Stacia
S
Rymarchyk
Christopher
C
Huston
Michael
M
Darsley
Beth D
BD
Kirkpatrick
D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000276:immunology*; D002169:Campylobacter Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology* / Q000517:prevention & control; D016123:Campylobacter jejuni / Q000276:immunology* / Q000472:pathogenicity*; D003967:Diarrhea / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D004341:Drug Evaluation / Q000379:methods*; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D006805:Human Experimentation; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007371:Interferon-gamma