Equally important, the same proteome array has also allowed us to identify eight antigens that were preferentially recognized by sera from the control group, thus designated as protection-associated antigens. The eight protection antigens are CT019, CT117, CT301, CT442, CT553, CT556, CT571, and CT709. Most of these proteins are highly conserved metabolic or modifying enzymes (CT019, CT301, CT553, CT709) or related to the general secretion pathway (CT571). The remaining three antigens are hypothetical proteins unique to
Chlamydia. CT117, consisting of 104 amino acids (aa) with a bilobal hydrophobic region and a pI of 8.21, is a putative inclusion membrane protein designated as IncF,
54,55 and IncF is highly immunogenic in women urogenitally infected with
C. trachomatis. 30,31 CT556, consisting of 159 aa with a putative transmembrane domain at its C-terminus and an acidic pI of 4.95, shares a low level of homology with a thiol:disulfide interchange protein DsbC of
Pseudomonas aeruginosa. 56 CT442 has been characterized as a cysteine-rich 15-kDa outer membrane protein, designated as CrpA.
57 CT442 is predicted to localize in the inclusion membrane
54 ; moreover, it contains a murine CD8
+ T-cell epitope that can elicit partial protective immunity to subsequent challenge with
C. trachomatis. 58 These three antigens (CT117, 442, and 556) appear to be suitable candidates for vaccine development, as they possess properties ideal for constructing an antitrachoma subunit vaccine: each are
Chlamydia-specific, likely localized in chlamydial organism or inclusion membrane, immunogenic in humans, and able to induce protective immunity. More than half a century ago, vaccination with formalin-fixed whole chlamydial organisms not only failed to induce long-lasting protective immunity against trachoma but also exacerbated ocular pathologies when some immunized children were exposed to natural infection.
59–62 These early observations might suggest that the formalin-fixed organisms not only had their protective antigen conformation altered by formalin fixation but also carried pathogenic antigens. Thus, a subunit vaccine by selecting protective antigens in their native conformation and excluding the pathogenic determinants may represent a promising approach for development of a vaccine to prevent trachomatous disease. Further evaluation of these
Chlamydia-specific protection-associated antigens for their ability to induce protective immunity in an appropriate model system should provide important information for developing a subunit vaccine against
C. trachomatis ocular infection and
C. trachomatis –induced ocular diseases.