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A Controlled Clinical Study of the Effect of Nasal Immunization with a Streptococcus mutans Antigen Alone or Incorporated into Liposomes on Induction of Immune Responses

机译:单独或掺入脂质体的变形链球菌抗原鼻腔免疫对诱导免疫反应的影响的对照临床研究

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Recent attention to mucosal immunization strategies has been focused on the nasal route for vaccine delivery. This study was designed to determine the effectiveness of a liposome-protein vaccine compared to that of a protein-only vaccine in inducing immune responses in humans. Healthy subjects were randomly assigned to two groups and immunized intranasally with a crude antigen preparation rich in glucosyltransferase (C-GTF) from Streptococcus mutans, alone or in liposomes. Parotid saliva, nasal wash, and serum were collected prior to and at weekly intervals following immunization and were analyzed for anti-C-GTF activity by enzyme-linked immunosorbent assay. The levels of immunoglobulin A (IgA) anti-C-GTF activity in the nasal wash from both groups after immunization increased to a mean peak of fivefold over the baseline level on day 28. Salivary IgA anti-C-GTF responses were induced to a lesser extent. IgG and IgA anti-C-GTF responses in serum were detected on day 14. The IgA responses were predominantly of the IgA1 subclass. These results show that C-GTF vaccines were more effective in inducing a local secretory IgA antibody response than a salivary or serum response when they were given intranasally. The IgA1 anti-C-GTF response in nasal wash samples for liposomal antigen versus antigen only was the only response which was significantly different (P < 0.04). This suggests that the form of the antigen affects the magnitude of the local mucosal response but not that of a disseminated response. These results provide evidence for the effective use of a nasal protein vaccine in humans for the induction of mucosal and systemic responses.
机译:最近对粘膜免疫策略的关注已集中在疫苗递送的鼻途径上。这项研究旨在确定脂质体蛋白疫苗与仅蛋白疫苗相比在诱导人类免疫应答中的有效性。将健康受试者随机分为两组,并分别用单独的或脂质体的,来自变形链球菌(em)的富含葡萄糖基转移酶(C-GTF)的粗制抗原制剂进行鼻内免疫。免疫前和免疫后每隔一周收集腮腺唾液,洗鼻液和血清,并通过酶联免疫吸附试验分析其抗C-GTF活性。免疫后,两组患者洗鼻液中的免疫球蛋白A(IgA)抗C-GTF活性水平在第28天均增加到基线水平的五倍平均峰。唾液IgA抗C-GTF应答被诱导为程度较轻。在第14天检测到血清中的IgG和IgA抗C-GTF应答。IgA应答主要是IgA1亚类。这些结果表明,鼻内给予C-GTF疫苗比唾液或血清反应更有效地诱导局部分泌型IgA抗体反应。鼻洗样品中的IgA1抗C-GTF应答对脂质体抗原与仅对抗原的应答是唯一显着不同的应答( P <0.04)。这表明抗原的形式影响局部粘膜反应的程度,但不影响扩散反应的程度。这些结果提供了在人中有效使用鼻蛋白疫苗诱导粘膜和全身反应的证据。

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