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首页> 外文期刊>Infection and immunity >Intranasal Delivery of Group B Meningococcal Native Outer Membrane Vesicle Vaccine Induces Local Mucosal and Serum Bactericidal Antibody Responses in Rabbits
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Intranasal Delivery of Group B Meningococcal Native Outer Membrane Vesicle Vaccine Induces Local Mucosal and Serum Bactericidal Antibody Responses in Rabbits

机译：B组脑膜炎球菌天然外膜囊泡疫苗的鼻腔递送可诱导兔的局部粘膜和血清杀菌抗体反应。

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We have previously shown that intranasal immunization of mice with meningococcal native outer membrane vesicles (NOMV) induces both a good local mucosal antibody response and a good systemic bactericidal antibody response. However, in the intranasal mouse model, some of the NOMV entered the lung and caused an acute granulocytic response. We therefore developed an alternate animal model using the rabbit. This model reduces the probability of lung involvement and more closely mimics intranasal immunization of humans. Rabbits immunized intranasally with doses of 100 μg of NOMV in 0.5 ml of saline developed serum bactericidal antibody levels comparable to those of rabbits immunized intramuscularly with 25-μg doses, particularly when the primary intranasal immunization was given daily for 3 days. Intranasal immunization also induced a local mucosal response as evidenced by immunoglobulin A antibody in saliva, nasal washes, and lung lavage fluids. NOMV from a capsule-deficient mutant induced higher serum bactericidal antibody responses than NOMV from the encapsulated parent. Meningococcal NOMV could be administered intranasally at 400 μg with no pyrogenic activity, but as little as 0.03 μg/kg of body weight administered intravenously or 25 μg administered intramuscularly induced a pyrogenic response. These data indicate that the rabbit is a useful model for preclinical testing of intranasal meningococcal NOMV vaccines, and this immunization regimen produces a safe and substantial systemic and local mucosal antibody response.
机译：我们以前已经表明，用脑膜炎球菌天然外膜囊泡（NOMV）对小鼠进行鼻内免疫可诱导良好的局部粘膜抗体应答和良好的全身杀菌抗体应答。但是，在鼻内小鼠模型中，一些NOMV进入肺部并引起急性粒细胞反应。因此，我们使用兔子开发了另一种动物模型。该模型降低了肺部受累的可能性，并更紧密地模拟了人类的鼻内免疫。在0.5 ml盐水中用100μgNOMV鼻腔内免疫的兔子产生的血清杀菌抗体水平与以25μg剂量肌内免疫的兔子相当，尤其是每天进行3天鼻腔初次免疫时。鼻内免疫还诱导局部黏膜反应，如唾液，鼻洗液和肺灌洗液中的免疫球蛋白A抗体所证明的。来自胶囊缺陷型突变体的NOMV比来自封装亲本的NOMV诱导更高的血清杀菌抗体反应。脑膜炎球菌NOMV可以400μg鼻内给药，无热原活性，但静脉内给药0.03μg/ kg体重或肌内注射25μg则可引起热原性应答。这些数据表明，该兔子是用于鼻内脑膜炎球菌NOMV疫苗临床前测试的有用模型，并且该免疫方案可产生安全且充分的全身和局部粘膜抗体应答。

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