title: Chlamydia trachomatis polymorphic membrane protein D is a species-common pan-neutralizing antigen.
abstract: Infections caused by the obligate intracellular pathogen Chlamydia trachomatis have a marked impact on human health. C. trachomatis serovariants are the leading cause of bacterial sexually transmitted disease and infectious preventable blindness. Despite decades of effort, there is no practical vaccine against C. trachomatis diseases. Here we report that all C. trachomatis reference serotypes responsible for sexually transmitted disease and blinding trachoma synthesize a highly conserved surface-exposed antigen termed polymorphic membrane protein D (PmpD). We show that Ab specific to PmpD are neutralizing in vitro. We also present evidence that Ab against serovariable-neutralizing targets, such as the major outer membrane protein, block PmpD neutralization. This finding suggests that a decoy-like immune evasion strategy may be active in vivo whereby immunodominant type-specific surface antigens block the neutralizing ability of species-common PmpD Ab. Collectively, these results show that PmpD is a previously uncharacterized C. trachomatis species-common pan-neutralizing target. Moreover, a vaccine protocol using recombinant PmpD to elicit neutralizing Ab in the absence of immunodominant type-specific Ab might be highly efficacious and surpass the level of protection achieved through natural immunity.
authors.affiliation: Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
authors.forename: Deborah D
authors.initials: DD
authors.lastname: Crane
authors.forename: John H
authors.initials: JH
authors.lastname: Carlson
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Fischer
authors.forename: Patrik
authors.initials: P
authors.lastname: Bavoil
authors.forename: Ru-ching
authors.initials: RC
authors.lastname: Hsia
authors.forename: Chun
authors.initials: C
authors.lastname: Tan
authors.forename: Cho-chou
authors.initials: CC
authors.lastname: Kuo
authors.forename: Harlan D
authors.initials: HD
authors.lastname: Caldwell
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000145:classification / Q000235:genetics / Q000276:immunology*; D001798:Blood Proteins / Q000276:immunology; D002460:Cell Line; D002692:Chlamydia trachomatis / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000648:ultrastructure; D016680:Genome, Bacterial / Q000235:genetics; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008854:Microscopy, Electron; D009500:Neutralization Tests; D011817:Rabbits; D017186:Titrimetry
chemical_list: D000906:Antibodies; D000941:Antigens; D001425:Bacterial Outer Membrane Proteins; D001798:Blood Proteins; D008070:Lipopolysaccharides