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Anti-bacterial and anti-toxic immunity induced by a killed whole-cell-cholera toxin B subunit cholera vaccine is essential for protection against lethal bacterial infection in mouse pulmonary cholera model.

Abstract
The lack of appropriate animal model for studying protective immunity has limited vaccine development against cholera. Here, we demonstrate a pulmonary cholera model conferred by intranasal administration of mice with live Vibrio cholerae. The bacterial components, but not cholera toxin, caused lethal and acute pneumonia by inducing massive inflammation. Intranasal immunization with Dukoral, comprising killed whole bacteria and recombinant cholera toxin B subunit (rCTB), developed both mucosal and systemic antibody responses with protection against the lethal challenge. Either rCTB-free Dukoral or rCTB alone partially protected the mice against the challenge. However, reconstitution of rCTB-free Dukoral with rCTB restored full protection. Parenteral immunization with Dukoral evoked strong systemic immunity without induction of mucosal immunity or protection from the challenge. These results suggest that both anti-bacterial and anti-toxic immunity are required for protection against V. cholerae-induced pneumonia, and this animal model is useful for pre-clinical evaluation of candidate cholera vaccines.
AuthorsS-S Kang, J S Yang, K W Kim, C-H Yun, J Holmgren, C Czerkinsky, S H Han
JournalMucosal immunology (Mucosal Immunol) Vol. 6 Issue 4 Pg. 826-37 (Jul 2013) ISSN: 1935-3456 [Electronic] United States
PMID23187318 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Bacterial
  • Cholera Vaccines
  • Vaccines, Inactivated
  • Cholera Toxin
Topics
  • Administration, Intranasal
  • Animals
  • Antibodies, Bacterial (immunology)
  • Cholera (microbiology, prevention & control)
  • Cholera Toxin (immunology)
  • Cholera Vaccines (administration & dosage, immunology)
  • Disease Models, Animal
  • Female
  • Immunity, Mucosal
  • Lung (immunology, microbiology)
  • Mice
  • Pneumonia (immunology, prevention & control)
  • Vaccines, Inactivated (administration & dosage, immunology)
  • Vibrio cholerae (immunology)

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