title: Assessment of the duration of protection in Campylobacter jejuni experimental infection in humans.
abstract: 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.
authors.affiliation: Naval Medical Research Center, Silver Spring, Maryland, USA. dtribble@usuhs.mil
authors.forename: David R
authors.initials: DR
authors.lastname: Tribble
authors.forename: Shahida
authors.initials: S
authors.lastname: Baqar
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Scott
authors.forename: Michael L
authors.initials: ML
authors.lastname: Oplinger
authors.forename: Fernando
authors.initials: F
authors.lastname: Trespalacios
authors.forename: David
authors.initials: D
authors.lastname: Rollins
authors.forename: Richard I
authors.initials: RI
authors.lastname: Walker
authors.forename: John D
authors.initials: JD
authors.lastname: Clements
authors.forename: Steven
authors.initials: S
authors.lastname: Walz
authors.forename: Paul
authors.initials: P
authors.lastname: Gibbs
authors.forename: Edward F
authors.initials: EF
authors.lastname: Burg
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Moran
authors.forename: Lisa
authors.initials: L
authors.lastname: Applebee
authors.forename: A Louis
authors.initials: AL
authors.lastname: Bourgeois
mesh_terms: 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
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007070:Immunoglobulin A; D007371:Interferon-gamma