Human Antibodies to PhtD, PcpA, and Ply Reduce Adherence to Human Lung Epithelial Cells and Murine Nasopharyngeal Colonization by Streptococcus pneumoniae
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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DOI：
10.1128/iai.02124-14
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发表时间：
2014-12-01
影响因子：
3.1
通讯作者：
Pichichero, Michael E.
中科院分区：
文献类型：
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作者：
Kaur, Ravinder;Surendran, Naveen;Pichichero, Michael E.
肺炎链球菌附着于人上皮细胞（HECs）是导致感染的发病机制的第一步。我们试图确定抗肺炎链球菌蛋白候选疫苗PhtD、PcpA和Ply的人抗体在体外和小鼠鼻咽（NP）体内阻止肺HECs粘附的作用。纯化人抗phtd、-PcpA和-Ply抗体，生成Fab片段。采用fab检测TIGR4和未包封菌株RX1对A549肺hec粘附的抑制作用。使用菌株TIGR4的等基因突变体检测单个蛋白在粘附中的作用。通过在小鼠模型中被动转移人抗体，评估了Anti-PhtD， -PcpA和-Ply人抗体在体内抑制NP定植的能力。人抗PhtD和PcpA抗体对A549细胞的粘附降低（P < 0.05）。抗phtd抗体对小鼠NP定殖具有保护作用，而非抗pcpa抗体。令我们惊讶的是，抗ply抗体也显著减少了肺炎链球菌的定植（P < 0.05）。我们的研究结果支持PhtD、PcpA和Ply蛋白候选疫苗作为结合疫苗的替代品，以防止非血清型特异性肺炎链球菌定植和侵袭性感染。
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.