Specific immune responses and enhancement of murine pulmonary clearance of Moraxella catarrhalis by intranasal immunization with a detoxified lipooligosaccharide conjugate vaccine
Specific immune responses and enhancement of murine pulmonary clearance of Moraxella catarrhalis by intranasal immunization with a detoxified lipooligosaccharide conjugate vaccine
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DOI：
10.1128/iai.70.11.5982-5989.2002
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发表时间：
2002-11-01
影响因子：
3.1
通讯作者：
Gu, XX
中科院分区：
文献类型：
--
作者：
Jiao, XN;Hirano, T;Gu, XX
卡他莫拉菌是一种重要的人类黏膜病原菌。本研究探讨了白喉毒素脱毒低聚糖交叉反应突变体(DLOS-CRM)疫苗候选疫苗滴鼻免疫对卡他毛虫气雾剂攻击后小鼠肺清除的影响。DLOS-CRM联合霍乱毒素滴鼻免疫小鼠后，鼻腔冲洗液、肺灌洗液、唾液和粪便中免疫球蛋白A(IgA)和免疫球蛋白G水平显著升高，且呈剂量依赖关系。此外，还检测了血清中抗卡他分支杆菌LOS的免疫球蛋白Ig G、Ig M和Ig A。用酶联免疫斑点法在鼻腔通道、脾、鼻腔相关淋巴组织、颈部淋巴结、肺和Peyer‘s斑块中发现了LOS特异性抗体形成细胞。与对照组相比，DLOS-CRM疫苗在肺部诱导了显著的同源和异源菌株的细菌清除(70%至90%)(P<；0.01)。有趣的是，与皮下注射DLOS-CRM相比，DLOS-CRM鼻腔免疫显示出更高的细菌清除水平。这些数据表明，DLOS-CRM通过鼻腔免疫诱导特异性粘膜和系统免疫，并提供有效的细菌清除。基于这些结果，我们认为DLOS-CRM应该继续进行测试，以确定它是否会在人体内诱导保护性免疫反应。
Moraxella catarrhalis is an important human mucosal pathogen. This study investigated the effect of intranasal immunization with a detoxified-lipooligosaccharide-cross-reactive mutant of diphtheria toxin (dLOS-CRM) vaccine candidate on pulmonary clearance following an aerosol challenge of mice with M. catarrhalis. Intranasal immunization with dLOS-CRM plus cholera toxin induced a significantly dose-dependent increase of immunoglobulin A (IgA) and IgG in the nasal wash, lung lavage fluid, saliva, and fecal extract. In addition, serum IgG, IgM, and IgA against LOS of M. catarrhalis were detected. LOS-specific antibody-forming cells were found in the nasal passages, spleens, nasally associated lymphoid tissues, cervical lymph nodes, lungs, and Peyer's patches using an enzyme-linked immunospot assay. The dLOS-CRM vaccine induced a significant bacterial clearance (70 to 90%) of both homologous and heterologous strains in the lungs compared to that observed in the controls (P < 0.01). Intriguingly, intranasal immunization with dLOS-CRM showed a higher level of bacterial clearance compared with subcutaneous injections with dLOS-CRM. These data indicate that dLOS-CRM induces specific mucosal and systemic immunity through intranasal immunization and also provides effective bacterial clearance. On the basis of these results, we believe that dLOS-CRM should undergo continued testing to determine whether it would induce protective immune response in humans.