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针对主要外膜蛋白可变域 4 线性表位的抗体与女性沙眼衣原体的清除或再感染无关。

Antibodies to Variable Domain 4 Linear Epitopes of the Major Outer Membrane Protein Are Not Associated with Chlamydia Resolution or Reinfection in Women.

机构信息

Department of Molecular Genetics and Microbiology, School of Medicine, University of New Mexico Health Sciences, Albuquerque, New Mexico, USA.

Department of Pathology, School of Medicine, University of New Mexico Health Sciences, Albuquerque, New Mexico, USA.

出版信息

mSphere. 2020 Sep 23;5(5):e00654-20. doi: 10.1128/mSphere.00654-20.

Abstract

is an obligate intracellular bacterium. infection is the most prevalent bacterial sexually transmitted infection and can lead to pelvic inflammatory disease and infertility in women. There is no licensed vaccine for prevention, in part due to gaps in our knowledge of -specific immune responses elicited during human infections. Previous investigations of the antibody response to have identified immunodominant antigens and antibodies that can neutralize infection in cell culture. However, epitope-specific responses to are not well characterized, and the impact of these antibodies on infection outcome is unknown. We recently developed a technology called deep sequence-coupled biopanning that uses bacteriophage virus-like particles to display peptides from antigens and affinity select against human serum IgG. Here, we used this technology to map -specific antibodies in groups of women with defined outcomes following infection: (i) negative upon presentation for treatment ("spontaneous resolvers"), (ii) negative at a 3-month follow-up visit after treatment ("nonreinfected"), and (iii) positive at a 3-month follow-up after treatment ("reinfected"). This analysis yielded immunodominant epitopes that had been previously described but also identified new epitopes targeted by human antibody responses to We focused on human antibody responses to the variable domain 4 serovar-conserved region of the major outer membrane protein (VD4-MOMP), a previously described immunodominant epitope. All three groups of women produced IgG to the VD4-MOMP, suggesting that detection of serum antibodies to VD4-MOMP in women with urogenital infection is not associated with protection against reinfection. infection is the most common bacterial sexually transmitted infection, and infection in women can lead to pelvic inflammatory disease and infertility. No licensed vaccine exists to prevent infection, and investigations of the natural immune response may inform the design of targeted vaccines for Our study fills a gap in knowledge regarding the epitope specificity of antibody responses that are elicited in response to infection in women. We identified several new B cell epitopes for antigens and confirmed B cell epitopes that have been identified by other methods. Our finding that women produce antibodies to the VD4-MOMP regardless of infection outcome provides insight into vaccine development, suggesting that vaccines targeting VD4-MOMP may need to elicit higher-titer antibody responses than natural infection imparts or that additional vaccine targets should be pursued in the future.

摘要

是一种专性细胞内细菌。 感染是最常见的细菌性性传播感染,可导致女性盆腔炎和不孕。目前尚无预防 的许可疫苗,部分原因是我们对人类感染期间引起的 -特异性免疫反应的了解存在差距。以前对 抗体反应的研究已经确定了免疫优势抗原和可以在细胞培养中中和感染的抗体。然而,针对 的表位特异性反应尚未得到很好的描述,并且这些抗体对感染结果的影响尚不清楚。我们最近开发了一种称为深度序列偶联生物淘选的技术,该技术使用噬菌体病毒样颗粒来展示抗原中的肽,并针对人血清 IgG 进行亲和选择。在这里,我们使用该技术对具有明确感染结果的女性群体中的 -特异性抗体进行了映射:(i)就诊时呈阴性(“自发清除者”),(ii)治疗后 3 个月随访时呈阴性(“未再感染者”),以及(iii)治疗后 3 个月随访时呈阳性(“再感染者”)。该分析产生了先前描述过的免疫显性表位,但也鉴定了针对 人类抗体反应的新表位。我们专注于人类对主要外膜蛋白(VD4-MOMP)可变域 4 血清型保守区的抗体反应,这是先前描述的免疫显性表位。所有三组女性均产生针对 VD4-MOMP 的 IgG,这表明在患有泌尿生殖道 感染的女性中检测血清中针对 VD4-MOMP 的抗体与防止再感染无关。 感染是最常见的细菌性性传播感染,感染会导致女性盆腔炎和不孕。目前尚无预防 的许可疫苗,对天然免疫反应的研究可能为 疫苗的靶向设计提供信息。我们的研究填补了女性中针对 感染引起的抗体反应的表位特异性知识空白。我们鉴定了针对 抗原的几个新的 B 细胞表位,并证实了其他方法鉴定的 B 细胞表位。我们发现,无论感染结果如何,女性都会产生针对 VD4-MOMP 的抗体,这为疫苗开发提供了深入的了解,表明针对 VD4-MOMP 的疫苗可能需要引发比自然感染更高滴度的抗体反应,或者未来需要寻求其他疫苗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2113/7568647/c9cc3cb62af4/mSphere.00654-20-f0001.jpg

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