Mucosal targeting and delivery of antigen is required for the induction of protective immunity against chlamydia. Modern vaccinology strives toward the exploitation of the cooperative interaction between immune inductive sites (i.e., draining lymphoid tissue(s) containing the primary APCs, such as DC, where an immune response is initiated) and immune effector sites (e.g., site of infection) to produce an optimal vaccine efficacy. By this approach, induction of optimal mucosal immunity requires targeting antigens to the specialized APCs of the mucosa-associated lymphoid tissues (MALT) in specific mucosal inductive sites [Wu & Russell, 1997]. MALT includes the nasal-associated lymphoid tissue (NALT), gut-associated lymphoid tissue (GALT), and bronchus-associated lymphoid tissue (BALT). Since the inductive and effector sites of the common mucosal immune system (CMIS) are compartmentalized, certain inductive and effector sites interact effectively to produce an optimal immune response [Wu & Russell, 1997]; hence, it is important to select a route of immunization that favors an effective cooperation between a given mucosal inductive site and a targeted mucosal effector site of infection. To optimize chlamydial vaccine efficacy, it is crucial to select a route of administration that targets the inductive sites producing high levels Th1 response in bronchial and oculogenital mucosae. Systemic immunization routes are not effective for inducing significant protective immunity in mucosal tissues [Holmgren et al., 1992; McGhee et al., 1992]. Intranasal immunization with live chlamydiae or with acellular outer membrane complex preparation induced protective chlamydial immunity [Pal et al., 1996; Pal et al., 1997], which correlated with rapid elicitation of a genital mucosal Th1 response, the CMI-associated IgG2a and secretory IgA [Igietseme et al., 1998]. Also, intranasal delivery of an experimental DNA-based vaccine protected against C. pneumoniae in a lung infection model [Svanholm et al., 2000]. Nasal immunization caused rapid generation of effector lymphocytes detectable within days of exposure [Wu et al., 1996] and was superior to vaginal, gastric, peritoneal, or rectal immunization for inducing mucosal anti-HIV or anti-HSV immune responses [Gallichan, 1995; Staats et al., 1997]. Therefore, in terms of compartmentalization within a CMIS, there is a strong link between NALT, BALT and the genital mucosa [Wu & Russell, 1997]. However, the APCs and other accessory cells in the mucosal inductive sites of NALT and the molecular pathways regulating trafficking, recruitment and maintenance of Th1 cells in the mucosal effector sites in BALT or oculogenital epithelia, remain undefined. Figures 7 and 8 show the influence of the route of presentation on the development of antichlamydial immune responses.

Among others, adhesion molecules, cytokines and chemokines will play a major role in these processes [Bonecchi et al., 1998]. Thus, the cellular and molecular basis for the temporary protective immunity following intravaginal chlamydial infection of mice includes the induction and retention of T cells in the genital mucosa [Igietseme & Rank, 1991], and involves the a4 b1-VCAM and the a4 b7-MAdCAM leukocyte adhesion pathways [Kelly & Rank; 1997; Igietseme et al., 2001].

Direct epithelial-T cell interaction via the ICAM1/LFA-1 pathway is also required for the efficient killing of intracellular chlamydiae in infected cells [Igietseme et al., 1996]. A better characterization of the molecular pathways and regulatory elements governing these processes in the inductive and effector sites of NALT, BALT and oculogenital mucosae could lend them to biochemical modulation to optimize immunity against Chlamydia and other agents of STDs. In addition to intranasal delivery, intramuscular route has been used successfully in experimental DNA immunizations against chlamydial respiratory infections [Brunham et al., 2000]. Moreover, intramuscular delivery of MOMP-ISCOMS or Vibrio cholerae ghosts expressing MOMP induced genital mucosal Th1 response and protected mice against genital challenge [Eko et al., 2001; Igietseme & Murdin, 2000]. Ultimately, different regimens may likely require different routes of immunization to target the inductive site(s) that induces optimal mucosal Th1 response.

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