Antigenic factors

The need for high frequency Th1 cells and the ancillary antibodies to successfully induce chlamydial immunity [Igietseme et al., 2002] indicates that an antigen with potential to induce protective immunity against chlamydia should possess adequate T cell and B cell epitopes. The physiochemical, biochemical and immunologic properties of an antigen would likely determine whether there are sufficient T cell epitopes to induce a high level Th1 response and the ancillary B cell function, or whether an immunopathogenic response is elicited. Experimental vaccine efforts using chlamydial outer membrane proteins, recombinant proteins, naked DNA, and ex vivo antigen pulsed dendritic cells in models of chlamydial genital and respiratory infections are revealing promising candidates. Thus, in addition to the major outer membrane protein (MOMP), which appears to possess both B and T cell epitopes, current efforts in chlamydial genomics and proteomics are identifying increasing vaccine candidates [Jen et al., 2001; Kalman et al., 1999; Stephens 2000; Stephens & Lammel 2001], with the polymorphic outer membrane proteins (POMP) and the conserved PorB family of membrane proteins being prominent [Rockey & Stephens, 2000; Stephens 2000; Stephens & Lammel 2001]. In fact, these efforts have identified an ADP/ATP translocase of C. pneumoniae as a protective antigen in a DNA delivery and mouse lung infection model [Murdin et al., 2000]. Comparative genomics analysis of these antigens should lead to the judicious selection of a combination of immunogens for a multi-subunit vaccine. The multiple subunit approach has the potential synergistic immunologic benefit of a combination of epitopes from multiple antigens, inducing a higher frequency of immune effectors that ensures an effective and long-lasting immunity. In addition to immunogenicity and ability to induce high frequency of Th1 cells, a potential subunit vaccine candidate aimed at wide acceptability should possess sufficient molecular and antigenic conservation to induce broad specificity, inducing heterotypic protection across species and serovars, and devoid of toxicity. The multisubunit approach increases the probability for heterotypic protection due to cross-reacting epitopes among different serovars. Lastly, while a number of potential chlamydial vaccine candidates are being reported, antigen selection based solely on surface recognition by antibodies will likely not be suitable for inducing protective immunity against chlamydia. Vaccine design efforts should therefore be cognizant of this requirement in order to achieve better success.

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