Evaluation of cholera vaccines formulated with toxin-coregulated pilin peptide plus polymer adjuvant in mice

Cholera is an acute diarrheal disease that is caused by the gram-negative b acterium Vibrio cholerae. The low efficacy of currently available killed-wh ole-cell vaccines and the reactinogenicity coupled with potential reversion of live vaccines have thus far precluded widespread vaccination for the co ntrol of cholera. Recent studies on the molecular nature of the virulence c omponents 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 in testine by V cholerae. In addition, polyclonal and several monoclonal antib odies directed against TCP have been shown to provide passive immunity to d isease in the infant mouse cholera model. In the present study, synthetic p eptides corresponding to portions of the C-terminal disulfide region of Tcp A pilin were formulated with polymer adjuvants currently in clinical trials and used to actively immunize adult female CD-1 mice. The experimental vac cine formulations elicited high levels of antigen-specific immunoglobulin G (IgG), including a broad spectrum of subclasses (IgG1, IgG2a, IgG2b, and I gG3), and lower levels of IgA. Infant mice born to the immunized mothers sh owed 100% protection against a 50% lethal dose (1 LD50) challenge and 50% p rotection against a 10-LD50 challenge with virulent strain O395. These resu lts indicate that specific regions of TcpA, including those delineated by t he peptides used in this study, have the potential to be incorporated into an effective defined subunit vaccine for cholera.