Assessment of the duration of protection in Campylobacter jejuni experimental infection in humans.
A human Campylobacter jejuni infection model provided controlled exposure to assess vaccine efficacy and investigate protective immunity for this important diarrheal pathogen. A well-characterized outbreak strain, C. jejuni 81-176, was investigated using a volunteer experimental infection model to evaluate the dose range and duration of protection. Healthy Campylobacter-seronegative adults received C. jejuni strain 81-176 via oral inoculation of 10(5), 10(7), or 10(9) CFU (5 adults/dose), which was followed by clinical and immunological monitoring. Based on dose range clinical outcomes, the 10(9)-CFU dose (n = 31) was used to assess homologous protection at 28 to 49 days (short-term veterans [STV]; n = 8) or 1 year (long-term veterans [LTV]; n = 7) after primary infection. An illness dose effect was observed for naïve subjects (with lower doses, 40 to 60% of the subjects were ill; with the 10(9)-CFU dose, 92% of the subjects were ill) along with complete protection for the STV group and attenuated illness for the LTV group (57%). Partial resistance to colonization was seen in STV (25% of the subjects were not infected; 3-log-lower maximum excretion level). Systemic and mucosal immune responses were robust in naïve subjects irrespective of the dose or the severity of illness. In contrast, in STV there was a lack of circulating antibody-secreting cells (ASC), reflecting the local mucosal effector responses. LTV exhibited comparable ASC responses to primary infection, and anamnestic fecal IgA responses likely contributed to self-resolving illness prior to antibiotic treatment. Campylobacter antigen-dependent production of gamma interferon by peripheral blood mononuclear cells was strongly associated with protection from illness, supporting the hypothesis that TH1 polarization has a primary role in acquired immunity to C. jejuni. This study revealed a C. jejuni dose-related increase in campylobacteriosis rates, evidence of complete short-term protection that waned with time, and immune response patterns associated with protection.
Tribble
David R
DR
Naval Medical Research Center, Silver Spring, Maryland, USA. dtribble@usuhs.mil
Baqar
Shahida
S
Scott
Daniel A
DA
Oplinger
Michael L
ML
Trespalacios
Fernando
F
Rollins
David
D
Walker
Richard I
RI
Clements
John D
JD
Walz
Steven
S
Gibbs
Paul
P
Burg
Edward F
EF
Moran
Anthony P
AP
Applebee
Lisa
L
Bourgeois
A Louis
AL
D000284:Administration, Oral; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002169:Campylobacter Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016123:Campylobacter jejuni / Q000276:immunology*; D003967:Diarrhea / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D005243:Feces / Q000737:chemistry; D005260:Female; D006805:Human Experimentation; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D012720:Severity of Illness Index; D013997:Time Factors; D055815:Young Adult
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007070:Immunoglobulin A; D007371:Interferon-gamma