Chitin micro-particles (CMP): A useful adjuvant for inducing viral specific immunity when delivered intranasally with an HIV-DNA vaccine
Chitin micro-particles (CMP): A useful adjuvant for inducing viral specific immunity when delivered intranasally with an HIV-DNA vaccine
复制标题
DOI：
10.1089/088282403771926355
复制
发表时间：
2003-01-01
期刊：
影响因子：
2.2
通讯作者：
Okuda, K
中科院分区：
文献类型：
--
作者：
Hamajima, K;Kojima, Y;Okuda, K
我们一直在研制一种基于HIV-1 env和rev表达质粒的HIV-DNA疫苗（20）。该疫苗与适当佐剂鼻内（内）给药可诱导小鼠产生高水平抗体（Ab），尤其是分泌型伊加（sIgA）Ab和HIV特异性细胞毒性T淋巴细胞（CTL）活性（7，23，31）。HIV特异性sIgA Ab是疫苗设计的一个重要方面，因为它能有效阻断HIV对粘膜的渗透，粘膜是包括HIV在内的几种病毒感染的主要部位。我们的研究小组和其他人已经报道粘膜伊加抑制HIV-1复制（3，8）。成功疫苗的第二个组成部分是诱导强CTL活性以有效消除病毒感染的细胞（6，30）。理想的HIV疫苗应该能够诱导强的粘膜和全身CTL活性。Strong等人报道，在小鼠过敏模型中鼻内施用来源于虾或蟹壳的几丁质微粒（CMP）显著减轻了由IL-12、IFN-g和TNF-α的上调引起的过敏症状（26）。柴田等人指出，甲壳素对产生抗分枝杆菌抗原的免疫力具有独特的Th 1佐剂作用（25）。其他天然Th 1增强剂，如热灭活的流产布鲁氏菌或CpG免疫刺激DNA序列，已被证明作为疫苗佐剂非常有效（10，13，32）。目前的研究旨在检查CMP是否具有佐剂作用，以及这是否可能对HIV-DNA疫苗的鼻腔接种有用。
WE HAVE BEEN DEVELOPING an HIV-DNA vaccine based on an HIV-1 env and rev expression plasmid (20). Intranasal (in) administration of this vaccine with an appropriate adjuvant induces high levels of antibody (Ab) production, especially secretory IgA (sIgA) Ab and HIV-specific cytotoxic T lymphocyte (CTL) activity in mice (7, 23, 31). HIV-specific sIgA Ab is an important aspect of vaccine design as it is effective at blocking HIV penetration of the mucosal membranes, which are the primary site for infection of several viruses including HIV. Our group and others have reported that mucosal IgA inhibits HIV-1 replication (3, 8). A second component of a successful vaccine is the induction of strong CTL activity for the efficient elimination of virus-infected cells (6, 30). An ideal HIV vaccine should be capable of inducing both strong mucosal and systemic CTL activity. Strong et al. reported that the intranasal application of chitin micro-particles (CMP) derived from shrimp or crab shells in mouse models of allergy markedly reduced allergic symptoms resulting from an up-regulation of IL-12, IFN-g and TNF-a (26). Shibata et al. indicated that chitin has a unique Th1 adjuvant effect on the development of immunity against a mycobacterial antigen (25). Other natural Th1 potentiators, such as heat-killed Brucella abortus or CpG immunostimulatory DNA sequences have proved very effective as vaccine adjuvants (10, 13, 32). The current study was designed to examine whether CMP has an adjuvant effect and whether this might be useful for nasal vaccination with HIV-DNA vaccine.