Intranasal immunization of mice with recombinant Streptococcus gordonii expressing NadA of Neisseria meningitidis induces systemic bactericidal antibodies and local IgA
Intranasal immunization of mice with recombinant Streptococcus gordonii expressing NadA of Neisseria meningitidis induces systemic bactericidal antibodies and local IgA
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DOI：
10.1016/j.vaccine.2008.05.049
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发表时间：
2008-08-05
期刊：
影响因子：
5.5
通讯作者：
Pozzi, Gianni
中科院分区：
文献类型：
--
作者：
Ciabattini, Annalisa;Giomarelli, Barbara;Pozzi, Gianni
将脑膜炎奈瑟菌B群的两种表面蛋白NadA和NhhA作为候选疫苗抗原，在人口腔链球菌表面表达。重组菌株通过鼻内途径免疫BALB/c小鼠，并评估局部和全身免疫应答。小鼠接种重组细菌单独或与LTR 72，大肠杆菌不耐热肠毒素的部分灭活突变体，作为粘膜佐剂。用表达NadA的活细菌进行鼻内免疫诱导了显著的血清抗体应答，IgG 2a亚类的流行率、71%动物血清中的杀菌活性以及鼻和支气管肺泡灌洗液中的NadA特异性伊加应答。福尔马林灭活的重组S.表达NadA的gordonii也鼻内给药，诱导与活细菌相当的全身和粘膜体液应答。施用重组细菌与粘膜佐剂LTR 72刺激更强的全身抗体应答，在85%的血清中具有保护性，而不增加局部伊加应答。重组变异链球菌表达NhhA的gordonii诱导了全身性而非粘膜抗体应答。这些数据支持NadA作为抗血清群B脑膜炎球菌的候选疫苗的作用，以及使用S. gordonii作为鼻内疫苗接种的载体。(C)2008爱思唯尔有限公司保留所有权利。
NadA and NhhA, two Surface proteins of serogroup B Neisseria meningitidis identified as candidate vaccine antigens, were expressed on the surface of the human oral commensal bacterium Streptococcus gordonii. Recombinant strains were used to immunize BALB/c mice by the intranasal route and the local and systemic immune response was assessed. Mice were inoculated with recombinant bacteria administered alone or with LTR72, a partially inactivated mutant of Escherichia coli heat-labile enterotoxin, as a mucosal adjuvant. Intranasal immunization with live bacteria expressing NadA induced a significant serum antibody response, with a prevalence of the IgG2a subclass, bactericidal activity in the sera of 71% of animals, and a NadA-specific IgA response in nasal and bronchoalveolar lavages. A formalin-inactivated recombinant strain of S. gordonii expressing NadA was also administered intranasally, inducing a systemic and mucosal humoral response comparable to that of live bacteria. The administration of recombinant bacteria with the mucosal adjuvant LTR72 Stimulated a stronger systemic antibody response, protective in 85% of sera, while did not increase the local IgA response. Recombinant S. gordonii expressing NhhA induced a systemic but not mucosal antibody response. These data support the role of NadA as vaccine candidate against serogroup B meningococci, and the use of S. gordonii as vector for intranasal vaccination. (C) 2008 Elsevier Ltd. All rights reserved.