Early human trials of candidate vaccines composed of the whole bacterial cell revealed that vaccinated individuals suffered exacerbated disease during subsequent infections [Grayston et al., 1985]. Thus, the use of whole chlamydial agents is unattractive due to the potential existence of immunopathogenic components [LaVerda et al., 1999]. In addition, despite the advantages of using an intact agent for designing vaccines against intracellular pathogens like Chlamydia, Mycobacteria, Listeria and Legionella [LaGrange et al., 1985; Su et al., 2000], in Chlamydia there are no stable genetic systems for successful transformation and no attenuated human strains have been developed, except for some preliminary reports that are yet to be extended [O'Connell & Maurelli, 1998]. Besides, only one report has demonstrated the isolation of C. trachomatis mutants [Wylie et al., 1996]. However, live attenuated C. psittaci strains have been developed and successfully protected ewes from chlamydia-induced abortion [Rodolakis et al., 1998], providing hope for future live attenuated human vaccines if the immunopathogenic concerns are alleviated. Nevertheless, the gradual shift in the philosophy of vaccine development from the classical whole agents to subunit, peptide or epitopic forms, and recent advances in chlamydial genomics and proteomics, would suggest that a subunit vaccine is achievable for chlamydia.

While the era of epitope or subunit vaccines have obviated the concerns inherent in inactivated or live-attenuated whole pathogens [Cohen & Brunham, 1999], modern vaccinology has also encountered a major set-back in the relatively poor immunogenicity of candidate subunit vaccines. Thus, the focus on a subunit chlamydial vaccine requires the development of more effective delivery vehicles, vector systems and adjuvants. The development of safe and effective delivery vehicles, such as adjuvants and vectors, or biological manipulations capable of boosting Th1 response and targeted to the genital or ocular mucosa [Stephens 2000], is a major goal in chlamydial research. Various strategies have been used to deliver chlamydial antigens to enhance immunogenicity and protective immunity. So far, most of the adjuvants have produced mixed results in various animal models of experimental chlamydial infections [Rank, 1999] as presented below. Therefore, development of effective and safe adjuvants and delivery vehicles remains an important objective in chlamydial vaccine.

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