Crane Deborah D, Carlson John H, Fischer Elizabeth R, Bavoil Patrik, Hsia Ru-ching, Tan Chun, Kuo Cho-chou, Caldwell Harlan D
Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1894-9. doi: 10.1073/pnas.0508983103. Epub 2006 Jan 30.
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.
由专性胞内病原体沙眼衣原体引起的感染对人类健康有显著影响。沙眼衣原体血清型是细菌性性传播疾病和感染性可预防失明的主要原因。尽管经过数十年努力，但仍没有针对沙眼衣原体疾病的实用疫苗。在此我们报告，所有导致性传播疾病和致盲性沙眼的沙眼衣原体参考血清型均合成一种高度保守的表面暴露抗原，称为多态膜蛋白D（PmpD）。我们表明，针对PmpD的抗体在体外具有中和作用。我们还提供证据表明，针对血清可变中和靶点（如主要外膜蛋白）的抗体可阻断PmpD的中和作用。这一发现表明，一种类似诱饵的免疫逃避策略可能在体内起作用，即免疫显性型特异性表面抗原会阻断种属共同的PmpD抗体的中和能力。总体而言，这些结果表明PmpD是一种以前未被表征的沙眼衣原体种属共同的泛中和靶点。此外，在没有免疫显性型特异性抗体的情况下，使用重组PmpD引发中和抗体的疫苗方案可能非常有效，并超过通过自然免疫所达到的保护水平。
