Journal
CLINICAL AND VACCINE IMMUNOLOGY
Volume 18, Issue 8, Pages 1371-1377Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/CVI.05088-11
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Funding
- ICDDR,B Centre for Health and Population Research
- International Research Scientist Development Award [KO1 TW07409, U01 AI058935, RO3 AI063079, U01 AI077883, KO1 TW07144]
- Charles H. Hood Foundation
- Howard Hughes Medical Institute
- Fogarty International Center [D43 TW05572]
- Fogarty International Center at the National Institutes of Health [D43 TW005572, R24 TW007988]
- Swedish Agency for International Development and Cooperation (Sida)
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Vibrio cholerae O1 is a noninvasive enteric pathogen and serves as a model for studies of mucosal immunity. Although symptomatic V. cholerae infection induces durable protection against subsequent disease, vaccination with oral killed whole-cell V. cholerae stimulates less long-lasting protection against cholera. In this study, we demonstrated that cholera induces an early proinflammatory cellular immune response that results in priming of Th1- and Th17-type cytokine responses to ex vivo antigenic stimulation and an increase in the ratio of Th1 to Th2 CD4(+) T-cell responses. Comparable priming of Th1 and Th17 responses, with an increased ratio of Th1 to Th2 CD4(+) T-cell responses, was not observed in subjects who received two doses of the oral cholera vaccine Dukoral (a whole-cell cholera toxin B subunit containing [WC-CTB] vaccine). These findings suggest that natural V. cholerae infection induces an early, proinflammatory cellular immune response, despite the apparent lack of clinical signs of inflammation. The failure of the WC-CTB vaccine to activate equivalent, CD4(+) T-cell responses is a potential explanation for the shorter duration of protection following immunization with this vaccine. Additional studies are needed to determine whether these early T-cell-mediated events predict the subsequent duration of immunologic memory.
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