A Genome-Wide Profiling of the Humoral Immune Response to Chlamydia trachomatis Infection Reveals Vaccine Candidate Antigens Expressed in Humans

Abstract

A whole genome scale proteome array consisting of 908 open reading frames encoded in Chlamydia trachomatis genome and plasmid was used to profile anti-chlamydial Ab responses. A total of 719 chlamydial proteins was recognized by one or more antisera from 99 women urogenitally infected with C. trachomatis. Revealing such a large C. trachomatis ANTIGENome in humans might partially be attributed to the significantly improved detection sensitivity of the whole genome scale proteome array assay because both linear and conformation-dependent Abs were detected by the array assay. Twenty-seven of the 719 Ags were recognized by ≥50% antisera, thus designated as immunodominant Ags. Comparison of Ag profiles recognized by live chlamydial organism-infected versus dead organism-immunized hosts led to the identification of infection-dependent or in vivo expressed Ags. The infection-dependent Ags induced Abs only in live organism-infected, but not in dead organism-immunized hosts. Many of these Ags were highly expressed during replication, but only minimally packaged into the infectious elementary bodies. Because inactivated whole chlamydial organism-based vaccines failed to induce protection in humans, identification of the infection-dependent or in vivo expressed immunodominant Ags in humans should greatly facilitate the selection of promising chlamydial subunit vaccine candidates for further evaluation. This approach may also be applicable to other pathogens.

Biochemical and Localization Analyses of Putative Type III Secretion Translocator Proteins CopB and CopB2 of Chlamydia trachomatis Reveal Significant Distinctions

“…Unfortunately, recombinant C. trachomatis CopB2 appears to be poorly antigenic (data not shown). This may also be the case with endogenous CopB2 during infection since antibody profiling studies of Chlamydia-infected humans fail to detect significant reactivity (54). After generating multiple CopB2-specific antibodies, we were unable to confirm inclusion membrane localization of endogenous CopB2.…”

Structure of the Chlamydia trachomatis Immunodominant Antigen Pgp3

“…Recent work reveals that the TNF-like domains are positioned distal to the exosporium anchor provided by the BclA NTD, suggesting that it is the TNF-like trimeric assembly that is adhesive and immunogenic (63). The TNF-like domain of Pgp3 is known to be the immunodominant antigen secreted during C. trachomatis infection (18,19). Thus far, few bacterial proteins have been demonstrated to possess TNF-like topology.…”

“…It is one of the most immunodominant antigens in mammals infected by chlamydial organisms (18,19). Human antibody recognition of Pgp3 is dependent on its trimeric quaternary structure (16).…”

Chlamydial Intracellular Survival Strategies

“…Cite this article as Cold Spring Harb Perspect Med 2013;3:a010256 www.perspectivesinmedicine.org (MOMP, OmcA, OmcB, and others) (reviewed in Hatch 1996), many of which are highly immunogenic (Wang et al 2010) and could possibly be recognized as PAMPs by cytosolic receptors. In addition, infected cells induce type I IFNs, which can activate cell-autonomous resistance mechanisms to Chlamydia (BernsteinHanley et al 2006).…”