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 ol' protection. healthy Campylobacter-seronegntive adults received C. jejuni strain 81-176 via oral inoculation of 105 , 107 , or 109 CFU (5 adults/dose), 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 [S'IV]; 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 S'IV (25% of the subjects were not infected; 3-log-lower maximum excretion level). Systemil' and mucosal immune responses were robust in na'ive subjects irrespective of the dose or the severity of illness. In contrast, in S'IV there was a lack of' circulating antibody-secreting cells (ASC), reflecting the local mucosal eft'ector 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2010
- Accession Number
- ADA551713
Entities
People
- Daniel A. Scott
- David R. Tribble
- David Rollins
- Fernando Trespalacios
- John D. Clements
- Michael L. Oplinger
- Richard L. Walker
- Shahida Baqar
- Steven Walz
Organizations
- Naval Medical Research Center