新鉴定的抗体可改进肺炎球菌疫苗设计

2011-09-26 06:46 · fiona

叶史瓦大学伯特爱因斯坦医学院的研究人员发现了一种抵抗肺炎球菌的新型抗体的作用方式。该发现将可用于改进抵抗肺炎的疫苗。

肺炎球菌

叶史瓦大学伯特爱因斯坦医学院的研究人员发现了一种抵抗肺炎球菌的新型抗体的作用方式。该发现将可用于改进抵抗肺炎的疫苗,研究成果发表在《American Society for Microbiology》的在线杂志mBio的9/10月刊上。

直到最近,科学家们还以为抵抗肺炎球菌的抗体是通过借助免疫细胞来杀死这些细菌的。但是,几年前,爱因斯坦医学院的研究者们发现,抗体即便不借助免疫细胞杀死病菌也对小鼠的实验性肺炎疾病非常有效。在最近的研究中,研究者们检测了这些抗体与肺炎球菌互相反应的方式,发现它们导致细菌凝结成块,增强了一种叫做群体感应的现象。

“群体感应是细菌群落与另外一个群落交流的一种方式,” 文章的主要作者Liise-anne Pirofski解释说道,“在这里,抗体增强细菌的群体感应的能力导致细菌表达能够杀死它们同类的基因,并使得细菌在不友好环境中存活并生存的防御机制变弱。”

国家传染病基金会估计,在美国每年有175000人因为肺炎球菌导致的肺炎而住院。此外,肺炎球菌每年还导致34500起血液感染和2200其脑膜炎病例。

两种肺炎球菌疫苗,一种用于成人,一种用于小孩和婴儿。通过保护接种疫苗的小孩及减少细菌在人与人之间的传播,小儿肺炎球菌结合疫苗能够显著减少小孩及成人中肺炎疾病的发病率。但是,疫苗不能对所有致病肺炎球菌起效,且现有用于成人的疫苗不能预防肺炎。对现有肺炎球菌疫苗进行加强,以降低肺炎球菌的自我保护能力,或者直接杀死它们可以增强这些抗体的有效性。

生物探索推荐英文论文摘要

Antibodies to Streptococcus pneumoniae Capsular Polysaccharide Enhance Pneumococcal Quorum Sensing

The use of pneumococcal capsular polysaccharide (PPS)-based vaccines has resulted in a substantial reduction in invasive pneumococcal disease. However, much remains to be learned about vaccine-mediated immunity, as seven-valent PPS-protein conjugate vaccine use in children has been associated with nonvaccine serotype replacement and 23-valent vaccine use in adults has not prevented pneumococcal pneumonia. In this report, we demonstrate that certain PPS-specific monoclonal antibodies (MAbs) enhance the transformation frequency of two different Streptococcus pneumoniae serotypes. This phenomenon was mediated by PPS-specific MAbs that agglutinate but do not promote opsonic effector cell killing of the homologous serotype in vitro. Compared to the autoinducer, competence-stimulating peptide (CSP) alone, transcriptional profiling of pneumococcal gene expression after incubation with CSP and one such MAb to the PPS of serotype 3 revealed changes in the expression of competence (com)-related and bacteriocin-like peptide (blp) genes involved in pneumococcal quorum sensing. This MAb was also found to induce a nearly 2-fold increase in CSP2-mediated bacterial killing or fratricide. These observations reveal a novel, direct effect of PPS-binding MAbs on pneumococcal biology that has important implications for antibody immunity to pneumococcus in the pneumococcal vaccine era. Taken together, our data suggest heretofore unsuspected mechanisms by which PPS-specific antibodies could affect genetic exchange and bacterial viability in the absence of host cells.

IMPORTANCE Current thought holds that pneumococcal capsular polysaccharide (PPS)-binding antibodies protect against pneumococcus by inducing effector cell opsonic killing of the homologous serotype. While such antibodies are an important part of how pneumococcal vaccines protect against pneumococcal disease, PPS-specific antibodies that do not exhibit this activity but are highly protective against pneumococcus in mice have been identified. This article examines the effect of nonopsonic PPS-specific monoclonal antibodies (MAbs) on the biology of Streptococcus pneumoniae. The results showed that in the presence of a competence-stimulating peptide (CSP), such MAbs increase the frequency of pneumococcal transformation. Further studies with one such MAb showed that it altered the expression of genes involved in quorum sensing and increased competence-induced killing or fratricide. These findings reveal a novel, previously unsuspected mechanism by which certain PPS-specific antibodies exert a direct effect on pneumococcal biology that has broad implications for bacterial clearance, genetic exchange, and antibody immunity to pneumococcus.

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