Newcastle Disease Virus-Like Particles Containing Respiratory Syncytial Virus G Protein Induced Protection in BALB/c Mice, with No Evidence of Immunopathology
Newcastle Disease Virus-Like Particles Containing Respiratory Syncytial Virus G Protein Induced Protection in BALB/c Mice, with No Evidence of Immunopathology
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DOI：
10.1128/jvi.01709-09
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发表时间：
2010-01-15
影响因子：
5.4
通讯作者：
Morrison, Trudy G.
中科院分区：
文献类型：
--
作者：
Murawski, Matthew R.;McGinnes, Lori W.;Morrison, Trudy G.
呼吸道合胞病毒（RSV）是儿童严重呼吸道感染的主要原因，也是老年人和免疫抑制人群的严重病因。目前还没有获得许可的疫苗可用于预防RSV疾病。我们已经开发了一种病毒样颗粒（VLP）候选疫苗，用于预防RSV。VLP由纽卡斯尔病病毒（NDV）的NP和M蛋白以及含有NDV HN蛋白的胞质和跨膜结构域以及人RSV G蛋白的胞外域（H/G）的嵌合蛋白组成。通过腹膜内或肌内接种用10或40 μ g总VLP-H/G蛋白免疫小鼠，刺激了对G蛋白的抗体应答，其与相当量的UV灭活RSV刺激的应答一样好或更好。用两个剂量或甚至单剂量的这些颗粒免疫小鼠导致小鼠完全免受肺部RSV复制的影响。用这些颗粒免疫诱导具有适度滴度的中和抗体。在VLP-H/G免疫的小鼠的RSV攻击后，没有观察到肺中的病理学增强，尽管用福尔马林灭活的RSV（FI-RSV）平行免疫的小鼠的肺显示出先前在用FI-RSV免疫后记录的显著病理学。因此，VLP-H/G候选疫苗在BALB/c小鼠中具有免疫原性，并可防止RSV在鼠肺中复制，无免疫病理学证据。这些数据支持进一步开发针对RSV的病毒样颗粒疫苗候选物。
Respiratory syncytial virus (RSV) is the leading cause of serious respiratory infections in children as well as a serious cause of disease in elderly and immunosuppressed populations. There are no licensed vaccines available to prevent RSV disease. We have developed a virus-like particle (VLP) vaccine candidate for protection from RSV. The VLP is composed of the NP and M proteins of Newcastle disease virus (NDV) and a chimeric protein containing the cytoplasmic and transmembrane domains of the NDV HN protein and the ectodomain of the human RSV G protein (H/G). Immunization of mice with 10 or 40 mu g total VLP-H/G protein by intraperitoneal or intramuscular inoculation stimulated antibody responses to G protein which were as good as or better than those stimulated by comparable amounts of UV-inactivated RSV. Immunization of mice with two doses or even a single dose of these particles resulted in the complete protection of mice from RSV replication in the lungs. Immunization with these particles induced neutralizing antibodies with modest titers. Upon RSV challenge of VLP-H/G-immunized mice, no enhanced pathology in the lungs was observed, although lungs of mice immunized in parallel with formalin-inactivated RSV (FI-RSV) showed the significant pathology that has previously been documented after immunization with FI-RSV. Thus, the VLP-H/G candidate vaccine was immunogenic in BALB/c mice and prevented replication of RSV in murine lungs, with no evidence of immunopathology. These data support further development of virus-like particle vaccine candidates for protection against RSV.