This same enhanced immunopathology effect is observed in mouse trials in animals given a live vaccine and then challenged with live organisms at a later date [86]. Recent studies have also suggested that some women, infected naturally at the genital tract site, can mount a level Z-VAD-FMK price of immunity against subsequent infections [87]. Indeed, these observations are extremely encouraging for the development of effective vaccines

as these individuals can be utilized to identify bio-profiles of protection (for humans) and then vaccine trials can attempt to induce these protective bio-profiles. The second issue, which is often not discussed, is that any protection is usually only short lived, with most vaccine trials only evaluating protection up to 4 weeks post vaccination. As a result of the issues surrounding crude, whole chlamydial vaccines, all efforts now involve the use of purified/cloned individual chlamydial antigens and virtually all of these studies have been conducted in the C. muridarum – mouse model. Indeed, while early vaccine efforts focussed very much on MOMP, and other surface antigens (e.g. Omp2), the past 5 years has seen a significant expansion in the number and type of antigens evaluated, including CPAF, PmpD, PmpG, CopN, IncA, NrdB and Pgp3 (many of which are intracellular proteins or at least not outer membrane proteins), in addition to the earlier favourites of MOMP, Omp2 and Hsp60 [42] (see

Table 1 for a list of all antigens that have been Pazopanib shown to induce an immune response following genital tract infection). Fig. 1(a) provides an overview of the chlamydial developmental cycle, including points of attack as well as vaccine candidates that have, or could be, tested for each of these stages. Progress towards identifying the “holy grail” vaccine antigen has been relatively slow, with next most new antigens evaluated only providing very modest, stepwise improvement in protection against live challenge.

The search for the best protective antigens though has become much more sophisticated recently, with groups directly identifying effective T cell antigens [88]. Brunham and colleagues are using an immunoproteomic screening approach to identify chlamydial antigens, or more correctly the actual T cell peptides, that are presented by C. muridarum-infected dendritic cells in the mouse model. Using this approach they have recently identified 13 Chlamydia peptides derived from eight novel epitopes presented by MHC class II molecules from bone marrow derived dendritic cells infected with Chlamydia. While some of the targets are new (RplF, FabG, AasF, ClpP-1, Gap, PmpE), interestingly, some overlap with previously identified antigens (PmpG). In addition to searching for the most highly protective vaccine candidate antigen, several groups now believe that a combination of antigens will be required. There are several lines of thought in compiling combination antigen vaccines. C.