The ultimate goal of functional immunobiology of chlamydial infection is to lay down the essential immunologic and immunomodulatory paradigms that can guide us to produce a safe immunization regimen capable of inducing a sterilizing, long-lived heterotypic protective immunity to control chlamydial infections and prevent the complications. This lofty goal continues to face enormous challenges that include identifying protective antigens, development of effective methods of vaccine delivery, construction of effective adjuvants and defining immunomodulatory strategies that will furnish an adequate immunologic environment for inducing and sustaining a high frequency of Th1 response. Research efforts leading to multi-subunit or a multi-component vaccine deserve emphasis. The effectiveness of the veterinary C. psittaci vaccine [Rodolakis et al., 1998], and the efficacy of the immunotherapeutic DC-based cellular vaccine using killed chlamydiae attest to the feasibility of an effective conventional vaccine. However, in designing a subunit vaccine, it will be crucial to identify and mimic those immunostimulatory properties of DC that mediate enhanced level of protective immunity. Thus, additional efforts should be aimed at: (i) the identification of vectors capable of stimulating and retaining a regional chlamydial-specific type 1 cellular immune response at the genital, respiratory or ocular mucosa, (ii) the identification of new antigens that are key targets of cellular immunity as well as B cell immunity, and (iii) the testing of candidate vaccines in pre-clinical animal models that are relevant to the targets of a vaccine in human infections of the eye, lung or genital tract. Furthermore, if a conventional vaccine becomes unattainable due to the complexity of chlamydia, it does not seem unreasonable, given the caveat of safety, to consider the use of attenuated chlamydial mutants as potential vaccines, if the immunopathogenic concerns can be alleviated. Since this approach requires modifying key chlamydial virulence factors, it awaits the development of a chlamydial transformation system capable of modifying or knocking out targeted chlamydial genes. Finally, a vaccine is the best approach to deliver long-lasting protection to the largest number of people worldwide. Therefore, while the ultimate goal of a chlamydial vaccine is ideally to achieve sterilizing immunity, a vaccine effective against disease sequelae, such as PID, blinding trachoma and tubal scarring would be acceptable as a first generation product. Moreover, the high-risk population for serious sequelae [Richey et al., 1999] might be the primary target of a vaccine that provides protection against complications.

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