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Infection and Immunity, December 2001, p. 7695-7702, Vol. 69, No. 12
Department of Microbiology and Immunology,
Dartmouth Medical School, Hanover, New Hampshire 03755
Received 7 May 2001/Returned for modification 3 July 2001/Accepted 24 August 2001
Cholera is an acute diarrheal disease that is caused by the
gram-negative bacterium Vibrio cholerae. The low
efficacy of currently available killed-whole-cell vaccines and
the reactinogenicity coupled with potential reversion of live vaccines
have thus far precluded widespread vaccination for the control of
cholera. Recent studies on the molecular nature of the virulence
components that contribute to V. cholerae pathogenesis
have provided insights into possible approaches for the development of
a defined subunit cholera vaccine. Genetic analysis has demonstrated
that the toxin-coregulated pilus (TCP) is the major factor that
contributes to colonization of the human intestine by V.
cholerae. In addition, polyclonal and several monoclonal
antibodies directed against TCP have been shown to provide passive
immunity to disease in the infant mouse cholera model. In the present
study, synthetic peptides corresponding to portions of the C-terminal
disulfide region of TcpA pilin were formulated with polymer adjuvants
currently in clinical trials and used to actively immunize adult female
CD-1 mice. The experimental vaccine formulations elicited high levels
of antigen-specific immunoglobulin G (IgG), including a broad spectrum
of subclasses (IgG1, IgG2a, IgG2b, and IgG3), and lower levels of IgA.
Infant mice born to the immunized mothers showed 100% protection
against a 50% lethal dose (1 LD50) challenge and 50%
protection against a 10-LD50 challenge with virulent strain
O395. These results indicate that specific regions of TcpA, including
those delineated by the peptides used in this study, have the potential
to be incorporated into an effective defined subunit vaccine for cholera.
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.12.7695-7702.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Evaluation of Cholera Vaccines Formulated with
Toxin-Coregulated Pilin Peptide Plus Polymer Adjuvant in Mice
*
Corresponding author. Mailing address: Dartmouth
Medical School, Department of Microbiology and Immunology, Vail
Building HB7550, Hanover, NH 03755. Phone: (603) 650-1632. Fax: (603)
650-1318. E-mail: ronald.k.taylor{at}dartmouth.edu.
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