Chlamydia trachomatis genome is predicted to encode a
type III secretion system consisting of more than 40 open reading frames (ORFs). To test whether these ORFs are expressed and immunogenic during chlamydial
infection in humans, we expressed 55 chlamydial ORFs covering all putative type III secretion components plus control molecules as fusion
proteins and measured the reactivity of these fusion
proteins with
antibodies from patients infected with C. trachomatis in the urogenital tract (24
antisera) or in the ocular tissue (8
antisera). Forty-five of the 55
proteins were recognized by at least 1 of the 32 human
antisera, suggesting that these
proteins are both expressed and immunogenic during chlamydial
infection in humans.
Tarp, a putative type III secretion effector
protein, was identified as a novel immunodominant
antigen due to its reactivity with the human
antisera at high frequency and titer. The expression and immunogenicity of
Tarp were confirmed in cell culture and mouse systems.
Tarp was mainly associated with the infectious form of chlamydial organisms and became undetectable between 13 and 24 h during the
infection cycle in cell culture. Mice intravaginally infected with C. muridarum developed
Tarp-specific humoral and cellular immune responses. More importantly, immunization of mice with
Tarp induced Th1-dominant immunity that significantly reduced the shedding of live organisms from the lower genital tract and attenuated inflammatory pathologies in the fallopian tube tissues. These observations have demonstrated that
Tarp, an immunodominant
antigen identified by human
antisera, can induce protective immunity against chlamydial
infection and pathology in mice.