3.9 Article

Comparison of Immune Responses to the O-Specific Polysaccharide and Lipopolysaccharide of Vibrio cholerae O1 in Bangladeshi Adult Patients with Cholera

Journal

CLINICAL AND VACCINE IMMUNOLOGY
Volume 19, Issue 11, Pages 1712-1721

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/CVI.00321-12

Keywords

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Funding

  1. ICDDR,B
  2. Intramural Research Program of the National Institutes of Health, NIDDK
  3. National Institutes of Health, National Institute of Allergy and Infectious Diseases [U01 AI058935, R03 AI063079, U01 AI077883, K08 AI100923, K08 AI089721]
  4. Fogarty International Center, Training Grant in Vaccine Development and Public Health [TW005572]
  5. American Recovery and Reinvestment Act (ARRA) Postdoctoral Fellowship in Global Infectious Diseases [TW05572]
  6. Career Development Awards [K01 TW07409, TW07144]
  7. Fogarty International Clinical Research Scholars Award [R24 TW007988]
  8. Swedish International Development Cooperation Agency
  9. Howard Hughes Medical Institute
  10. American Society for Tropical Medicine & Hygiene-Burroughs Wellcome Fund
  11. Harvard Institute for Global Health Postdoctoral Fellowship in Global Infectious Diseases

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Immunity against Vibrio cholerae O1 is serogroup specific, and serogrouping is defined by the O-specific polysaccharide (OSP) part of lipopolysaccharide (LPS). Despite this, human immune responses to V. cholerae OSP have not previously been characterized. We assessed immune responses against V. cholerae OSP in adults with cholera caused by V. cholerae O1 El Tor serotype Inaba or Ogawa in Dhaka, Bangladesh, using O1 OSP-core-bovine serum albumin (OSPc:BSA) conjugates; responses targeted OSP in these conjugates. Responses of Inaba-infected patients to Inaba OSP and LPS increased significantly in IgG, IgM, and IgA isotypes from the acute to convalescent phases of illness, and the responses correlated well between OSP and LPS (R = 0.86, 0.73, and 0.91, respectively; P < 0.01). Plasma IgG, IgM, and IgA responses to Ogawa OSP and LPS in Ogawa-infected patients also correlated well with each other (R = 0.60, 0.60, and 0.92, respectively; P < 0.01). Plasma IgM responses to Inaba OSP and Ogawa OSP correlated with the respective serogroup-specific vibriocidal antibodies (R = 0.80 and 0.66, respectively; P < 0.001). Addition of either OSPc: BSA or LPS, but not BSA, to vibriocidal assays inhibited vibriocidal responses in a comparable and concentration-dependent manner. Mucosal IgA immune responses to OSP and LPS were also similar. Our study is the first to characterize anti-OSP immune responses in patients with cholera and suggests that responses targeting V. cholerae LPS, including vibriocidal responses that correlate with protection against cholera, predominantly target OSP. Induction of anti-OSP responses may be associated with protection against cholera, and our results may support the development of a vaccine targeting V. cholerae OSP.

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