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首页> 外文期刊>Infection and immunity >Intranasal Administration of a Meningococcal Outer Membrane Vesicle Vaccine Induces Persistent Local Mucosal Antibodies and Serum Antibodies with Strong Bactericidal Activity in Humans
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Intranasal Administration of a Meningococcal Outer Membrane Vesicle Vaccine Induces Persistent Local Mucosal Antibodies and Serum Antibodies with Strong Bactericidal Activity in Humans

机译：脑膜炎球菌外膜囊泡疫苗的鼻内给药可诱导持久的局部粘膜抗体和具有较强杀菌活性的血清抗体

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A nasal vaccine, consisting of outer membrane vesicles (OMVs) from group B Neisseria meningitidis, was given to 12 volunteers in the form of nose drops or nasal spray four times at weekly intervals, with a fifth dose 5 months later. Each nasal dose consisted of 250 μg of protein, equivalent to 10 times the intramuscular dose that was administered twice with a 6-week interval to 11 other volunteers. All individuals given the nasal vaccine developed immunoglobulin A (IgA) antibody responses to OMVs in nasal secretions, and eight developed salivary IgA antibodies which persisted for at least 5 months. Intramuscular immunizations did not lead to antibody responses in the secretions. Modest increases in serum IgG antibodies were obtained in 5 volunteers who had been immunized intranasally, while 10 individuals responded strongly to the intramuscular vaccine. Both the serum and secretory antibody responses reached a maximum after two to three doses of the nasal vaccine, with no significant booster effect of the fifth dose. The pattern of serum antibody specificities against the different OMV components after intranasal immunizations was largely similar to that obtained with the intramuscular vaccine. Five and eight vaccinees in the nasal group developed persistent increases in serum bactericidal titers to the homologous meningococcal vaccine strain expressing low and high levels, respectively, of the outer membrane protein Opc. Our results indicate that meningococcal OMVs possess the structures necessary to initiate systemic as well as local mucosal immune responses when presented as a nasal vaccine. Although the serum antibody levels were less conspicuous than those after intramuscular vaccinations, the demonstration of substantial bactericidal activity indicates that a nonproliferating nasal vaccine might induce antibodies of high functional quality.
机译：鼻疫苗由B组脑膜炎奈瑟氏球菌的外膜囊泡（OMV）组成，以滴鼻剂或鼻喷雾剂的形式每周12次以12次志愿者的形式给予鼻腔疫苗，剂量为5几个月后。每个鼻腔剂量由250μg蛋白质组成，相当于以6周为间隔向11名其他志愿者两次肌肉注射剂量的10倍。接受鼻疫苗的所有个体对鼻分泌物中的OMV产生免疫球蛋白A（IgA）抗体反应，而八种唾液IgA抗体持续至少5个月。肌内免疫未导致分泌物中的抗体反应。在5位经鼻内免疫的志愿者中，血清IgG抗体适度增加，而10位个体对肌内疫苗反应强烈。 2-3剂鼻疫苗后，血清抗体和分泌抗体反应均达到最大，而第五剂没有明显的增强作用。鼻内免疫后，针对不同OMV组分的血清抗体特异性模式与肌肉注射疫苗基本相似。与分别表达低和高水平外膜蛋白Opc的同源脑膜炎球菌疫苗株相比，鼻腔组中的五种和八种疫苗的血清杀菌力持续升高。我们的结果表明，作为鼻疫苗时，脑膜炎球菌OMV具有启动全身及局部粘膜免疫反应所必需的结构。尽管血清抗体水平不如肌肉注射疫苗后明显，但具有明显的杀菌活性表明，不扩散的鼻疫苗可能会诱导高功能质量的抗体。

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