| It is known that 95% cases of infection take place in mucosa, especially the respiratory and alimentary tract. It has to face the outer environment at first hand. Thus it is unremitting exposed to enormous varied antigens, including pathogens. Thereby the mucosa becomes the most common route that infections take place and vaccines should be inoculated. The mucosal immune mechanism has its special characteristics compared to that of systematic immunity. As the understanding of mucosal characteristics deeper and deeper, mocosal vaccine and mucosal inoculation become the hotspot of immunology and prophylactic medicine. It is the very important theoretic basis of vaccine construction and promotion and the immune program establishment. Utilization of mucosal vaccination can provide resolution means to some insurmountability existing in gene vaccine and gene therapy, which hopes to be solved through mucosal vector and mucosal administration. So it wins the researchers' favor in this field. It is very important to do more research on the mucosal immune protective mechanism and mocosal vacines' capability for carrying foreign antigens or DNAs into bodies. Then the immune responses and protective mechanism were explored in different animal models, different mocosal vaccination routes with the two types bivalent shigella vaccines constructed by our laboratory, and the possibility as an effective foreign DNA plasmids delivery vectors of the vaccines were detected in this paper.FSM-2117 and FS-5416 (FS-5402, 5411, 5414) are two types bivalent shigella vaccines of S. flexneri and S. sonnei constructed by our laboratory, one type (FSM-2117) is non-invasive and the other invasive. The common characteristic of them is that both of them expressed the LPS-O antigens of S. flexneri and S. sonnei, and the difference between them is that four kinds invasive proteins (IpaA, B, C, D, Ipa+) are expressed by the latter and hemolysis positive and invasive (inv+) while the former does not. To explore mucosal immune protection mechanism of vaccines (Ipa- and Ipa+) by different routes, and their possibility of being mucosal vectors for delivery foreign DNA plasmid, the immune responses and the immune protection effects were observed, then the mucosal delivery vectors were constructed with the vaccines (FSM-2117, FS-5416 and Ty21a) and TRAIL(TNF-related apoptosis inducing ligand) eukaryotic expressing systems, and the gene therapeutic effects ofthe vectors were observed. It was found that the two types shigella vaccines both brought about significant changes of specific bivalent antibodies levels in local mucosa site and system, by different mucosal vaccination routes and that the influences on the immune responses and immne protection with the expression of Ipa in the two shigella vaccines and by different mucosal routes administration. Then shigella vaccine and typhi vaccine TRAIL gene therapeutic vectors were constructed, and expression of the TRAIL in vivo and their suppression to tumor were detected. The main results are that:(1) The levels of specific bivalent IgA and IgG against S. flexneri 2a and S. sonnei LPS in the local mucosa sites and the system were rising significantly after inoculation with the two phenotypes(Ipa- and Ipa+) shigella vaccines through different mucosal routes including intranasal, intraocular and intragastric administration compared with the control. slgA predominates in the mucosal sites while it is IgG in the serum, which means that both bivalent vaccines have potent immunogenity. Moreover, expression of Ipa could promote the rising of the level of specific antibodies by intranasal vaccination and induce more effective common mucosal immunity reactions.(2) It is that not only effective local and common mucosal immune reactions were found, especially antibodies responses in genital tract, but also strong systematic antibodies responses were induced by intranasal inoculation with two phenotypes bivalent shigella vaccines in a low dose in mice. And high doses were needed to stim...
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