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首页> 外文期刊>Infection and immunity >Human Antibodies to PhtD, PcpA, and Ply Reduce Adherence to Human Lung Epithelial Cells and Murine Nasopharyngeal Colonization by Streptococcus pneumoniae
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Human Antibodies to PhtD, PcpA, and Ply Reduce Adherence to Human Lung Epithelial Cells and Murine Nasopharyngeal Colonization by Streptococcus pneumoniae

机译：人类对PhtD，PcpA和Ply的抗体可减少对人肺上皮细胞的粘附和肺炎链球菌对小鼠鼻咽的定植

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Streptococcus pneumoniae adherence to human epithelial cells (HECs) is the first step in pathogenesis leading to infections. We sought to determine the role of human antibodies against S. pneumoniae protein vaccine candidates PhtD, PcpA, and Ply in preventing adherence to lung HECs in vitro and mouse nasopharyngeal (NP) colonization in vivo. Human anti-PhtD, -PcpA, and -Ply antibodies were purified and Fab fragments generated. Fabs were used to test inhibition of adherence of TIGR4 and nonencapsulated strain RX1 to A549 lung HECs. The roles of individual proteins in adherence were tested using isogenic mutants of strain TIGR4. Anti-PhtD, -PcpA, and -Ply human antibodies were assessed for their ability to inhibit NP colonization in vivo by passive transfer of human antibody in a murine model. Human antibodies generated against PhtD and PcpA caused a decrease in adherence to A549 cells (P < 0.05). Anti-PhtD but not anti-PcpA antibodies showed a protective role against mouse NP colonization. To our surprise, anti-Ply antibodies also caused a significant (P < 0.05) reduction in S. pneumoniae colonization. Our results support the potential of PhtD, PcpA, and Ply protein vaccine candidates as alternatives to conjugate vaccines to prevent non-serotype-specific S. pneumoniae colonization and invasive infection.
机译：肺炎链球菌对人上皮细胞（HEC）的粘附是导致感染的发病机理的第一步。我们试图确定针对肺炎链球菌蛋白疫苗候选药物PhtD，PcpA和Ply的人抗体在预防肺HEC的体外粘附和小鼠鼻咽（NP）体内定殖的作用/ em>。纯化人抗PhtD，-PcpA和-Ply抗体，并生成Fab片段。 Fab被用于测试TIGR4和未包囊的菌株RX1对A549肺HEC的粘附抑制。使用菌株TIGR4的同基因突变体测试了单个蛋白质在粘附中的作用。通过在鼠模型中被动转移人抗体来评估抗PhtD，-PcpA和-Ply人抗体在体内抑制NP定植的能力。针对PhtD和PcpA产生的人类抗体导致对A549细胞的依从性降低（ P <0.05）。抗PhtD抗体而非抗PcpA抗体显示出对小鼠NP定植的保护作用。令我们惊讶的是，抗Ply抗体还导致肺炎链球菌定植的幅度大大降低（ P <0.05）。我们的结果支持了PhtD，PcpA和Ply蛋白疫苗候选物作为结合疫苗替代品的潜力，以预防非血清型特异性肺炎链球菌定植和侵袭性感染。

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