Assessment of the duration of protection in campylobacter jejuni experimental infection in humans
Tribble, D. R. Baqar, S. Scott, D. A. Oplinger, M. L. Trespalacios, F. Rollins, D. Walker, R. I. Clements, J. D. Walz, S. Gibbs, P.
Tribble, D. R.
Baqar, S.
Scott, D. A.
Oplinger, M. L.
Trespalacios, F.
Rollins, D.
Walker, R. I.
Clements, J. D.
Walz, S.
Gibbs, P.
Publication Date
2010-01-19
Type
Article
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Citation
Tribble, D. R. Baqar, S.; Scott, D. A.; Oplinger, M. L.; Trespalacios, F.; Rollins, D.; Walker, R. I.; Clements, J. D.; Walz, S.; Gibbs, P.; Burg, E. F.; Moran, A. P.; Applebee, L.; Bourgeois, A. L. (2010). Assessment of the duration of protection in campylobacter jejuni experimental infection in humans. Infection and Immunity 78 (4), 1750-1759
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 naive 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 naive 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.
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Publisher
American Society for Microbiology
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Attribution-NonCommercial-NoDerivs 3.0 Ireland