Chlamydia trachomatis polymorphic membrane protein D is a species-common pan-neutralizing antigen.
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.
Crane
Deborah D
DD
Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Carlson
John H
JH
Fischer
Elizabeth R
ER
Bavoil
Patrik
P
Hsia
Ru-ching
RC
Tan
Chun
C
Kuo
Cho-chou
CC
Caldwell
Harlan D
HD
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
D000906:Antibodies; D000941:Antigens; D001425:Bacterial Outer Membrane Proteins; D001798:Blood Proteins; D008070:Lipopolysaccharides