Enhancement of protective efficacy following intranasal immunization with vaccine plus a nontoxic LTK63 mutant delivered with nanoparticles

Enhancement of protective efficacy following intranasal immunization with vaccine plus a nontoxic LTK63 mutant delivered with nanoparticles
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DOI:
10.1128/iai.70.9.4785-4790.2002
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发表时间:
2002-09-01
影响因子:
3.1
通讯作者:
Del Giudice, G
Del Giudice, G
中科院分区:
医学2区
文献类型:
--
作者:
Baudner, BC;Balland, O;Del Giudice, G

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大多数疫苗仍然是非肠道接种。粘膜疫苗接种将提供不同于非肠道免疫的优势,包括在进入的入口处阻断病原体。本文研究了无毒大肠杆菌不耐热肠毒素(LT)突变体和超分子生物载体系统(SMBV)分别作为黏膜佐剂和给药系统对C群脑膜炎球菌结合疫苗进行鼻腔免疫的效果。与LT突变体和SMBV共同研制的结合疫苗诱导了非常高滴度的针对C组脑膜炎双球菌多糖的血清和粘膜抗体。这种疫苗接种策略还诱导了高滴度的具有杀菌活性的抗体,这是已知与疗效相关的。重要的是,粘膜接种,而不是传统的非肠道接种,在粘膜水平上诱导杀菌抗体。这些数据有力地支持了开发鼻腔疫苗的可行性,该疫苗对脑膜炎球菌具有增强的保护效力,并可能对其他被包裹的细菌具有增强的保护效力。
Most vaccines are still given parenterally. Mucosal vaccination would offer different advantages over parenteral immunization, including blocking of the pathogens at the portal of entry. In this paper, nontoxic Escherichia coli heat-labile enterotoxin (LT) mutants and Supramolecular Biovector systems (SMBV) were evaluated in mice as mucosal adjuvants and delivery systems, respectively, for intranasal immunization with the conjugated group C meningococcal vaccine. The conjugated vaccine formulated together with the LT mutants and the SMBV induced very high titers of serum and mucosal antibodies specific for the group C meningococcal polysaccharide. This vaccination strategy also induced high titers of antibodies with bactericidal activity, which is known to correlate with efficacy. Importantly, the mucosal vaccination, but not the conventional parenteral vaccination, induced bactericidal antibodies at the mucosal level. These data strongly support the feasibility of development of intranasal vaccines with an enhanced protective efficacy against meningococci and possibly against other encapsulated bacteria.