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Infection and Immunity, October 2008, p. 4554-4563, Vol. 76, No. 10
0019-9567/08/$08.00+0     doi:10.1128/IAI.00532-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Immunization with Vibrio cholerae Outer Membrane Vesicles Induces Protective Immunity in Mice{triangledown}

Stefan Schild,1,2 Eric J. Nelson,1 and Andrew Camilli1*

Howard Hughes Medical Institute and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts 02111,1 Institut fuer Molekulare Biowissenschaften, Karl-Franzens-Universitaet Graz, Humboldtstrasse 50, 8010 Graz, Austria2

Received 30 April 2008/ Returned for modification 16 June 2008/ Accepted 21 July 2008

The gram-negative bacterium Vibrio cholerae releases outer membrane vesicles (OMVs) during growth. In this study, we immunized female mice by the intranasal, intragastric, or intraperitoneal route with purified OMVs derived from V. cholerae. Independent of the route of immunization, mice induced specific, high-titer immune responses of similar levels against a variety of antigens present in the OMVs. After the last immunization, the half-maximum total immunoglobulin titer was stable over a 3-month period, indicating that the immune response was long lasting. The induction of specific isotypes, however, was dependent on the immunization route. Immunoglobulin A, for example, was induced to a significant level only by mucosal immunization, with the intranasal route generating the highest titers. We challenged the offspring of immunized female mice with V. cholerae via the oral route in two consecutive periods, approximately 30 and 95 days after the last immunization. Regardless of the route of immunization, the offspring was protected against colonization with V. cholerae in both challenge periods. Our results show that mucosal immunizations via both routes with OMVs derived from V. cholerae induce long-term protective immune responses against this gastrointestinal pathogen. These findings may contribute to the development of "nonliving," OMV-based vaccines against V. cholerae and other enteric pathogens, using the oral or intranasal route of immunization.

* Corresponding author. Mailing address: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111. Phone: (617) 636-2144. Fax: (617) 636-2175. E-mail: andrew.camilli{at}tufts.edu

{triangledown} Published ahead of print on 4 August 2008.

Editor: B. A. McCormick

Infection and Immunity, October 2008, p. 4554-4563, Vol. 76, No. 10
0019-9567/08/$08.00+0     doi:10.1128/IAI.00532-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Schild, S., Nelson, E. J., Bishop, A. L., Camilli, A. (2009). Characterization of Vibrio cholerae Outer Membrane Vesicles as a Candidate Vaccine for Cholera. Infect. Immun. 77: 472-484 [Abstract] [Full Text]  


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