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.
Tribble
David R
DR
Department of Enteric Diseases, Naval Medical Research Center, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Baqar
Shahida
S
Carmolli
Marya P
MP
Porter
Chad
C
Pierce
Kristen K
KK
Sadigh
Katrin
K
Guerry
Patricia
P
Larsson
Catherine J
CJ
Rockabrand
David
D
Ventone
Cassandra H
CH
Poly
Frederic
F
Lyon
Caroline E
CE
Dakdouk
Sandra
S
Fingar
Ann
A
Gilliland
Theron
T
Daunais
Patrick
P
Jones
Erika
E
Rymarchyk
Stacia
S
Huston
Christopher
C
Darsley
Michael
M
Kirkpatrick
Beth D
BD
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