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Assessment of the Duration of Protection in Campylobacter jejuni Experimental Infection in Humans
NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD
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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 ol protection. healthy Campylobacter-seronegntive adults received C. jejuni strain 81-176 via oral inoculation of 105 , 107 , or 109 CFU 5 adultsdose, which was followed hy clinical and immunological monitoring. Based on dose range clinical outcomes, the 109-CFU dose II 31 was used to assess homologous protection at 28 to 49 days short-term veterans SIV n 8 or 1 year long-term veterans L1V 7 after primary infection. An illness dose effect was observed for naive subjects with lower doses, 40 to 60 of the subjects were ill with the 109 -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 SIV 25 of the subjects were not infected 3-log-lower maximum excretion level. Systemil and mucosal immune responses were robust in naive subjects irrespective of the dose or the severity of illness. In contrast, in SIV there was a lack of circulating antibody-secreting cells ASC, reflecting the local mucosal eftector responses. L1V exhibited comparable ASC responses to primary infection, and anamnestic fecal lgA responses likely contributed to self-resolving illness prior to antibiotic treatment. Cnmpylobacter antigen-dependent production of gamma interferon by peripheral blood mononuclear cells was strongly associated with protection from illness, supporting the hypothesis that THI polarization has a primary role in acquired immunity to C. jejuni.
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