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1.
腺病毒载体在疫苗研究中的应用   总被引:1,自引:0,他引:1  
以病毒为载体的活疫苗为疾病预防和治疗研究提供了新手段。目前用于疫苗研究的病毒载体主要包括痘苗病毒载体、腺病毒载体、腺相关病毒载体、单纯疱疹病毒载体及逆转录病毒载体等。其中,重组腺病毒载体因其基因组大小适中,易于基因重组操作,繁殖滴度高,易于大量制备和保存,宿主范围广,转导效率高,安全性好,能刺激机体产生强烈的体液和细胞免疫反应等特点,而被广泛应用于重要感染性疾病及恶性肿瘤的疫苗研究。腺病毒载体在人免疫缺陷病毒(HIV)疫苗研究和临床试验中的成败更是备受关注。然而,与其他载体疫苗一样,机体对载体的免疫反应仍是阻碍腺病毒载体疫苗在临床中广泛应用的主要问题。那么,腺病毒载体解决这类问题的优势何在?我们简要综述腺病毒载体的特点及其在疫苗研究中的应用和存在的问题,为进一步优化和利用腺病毒载体在疫苗方面的研究提供参考。  相似文献   

2.
腺病毒本身作为疫苗和作为抗原呈递载体都是疫苗研究的热点。我们对国内外腺病毒疫苗的研究现状进行了简要综述,对应用腺病毒作为抗原和表位呈递载体的主要设计和研究思路及最新进展做了总结分析。  相似文献   

3.
痘苗病毒载体研究和应用虽多,但国际卫生组织(WHO)已宣布全球消灭天花可不再种痘,加之该病毒用于生物体后可以引起机体发生免疫排斥反应,限制了目的基因在生物体内长期有效的表达,也给重复接种带来困难,而且痘苗病毒对生物体还具有一定毒性作用,人类种痘偶尔产生严重副反应,从而限制了其使用范围。目前在改造腺病毒基因组方面已取得明显进展,证明腺病毒是基因工程疫苗的重要载体,倾向于以腺病毒为表达载体发展多价重组口服活疫苗,尤其在乙型肝炎和狂犬病疫苗研制上成效卓著,安全的腺病毒载体疫苗必将产生并成功地得到临床应用。本文着重从腺病毒载体构建,人和犬腺病毒载体重  相似文献   

4.
腺病毒载体已经成为基因工程疫苗及癌症、遗传病基因治疗的重要工具。腺病毒可分为哺乳动物腺病毒和禽腺病毒,禽腺病毒包括20多个血清型,分别归属于三个群:Ⅰ群为传统的禽腺病毒(FAV),Ⅱ群包括火鸡出血性肠炎病毒(HEV)等,Ⅲ群禽腺病毒为减蛋综合征病毒(EDSV)。这些病毒广泛地存在于多种禽类的呼吸道、消化道,大多呈显性或不显性感染。以禽类腺病毒为载体表达禽类重要病原的保护性抗原基因,构建多价(联)活载体基因工程疫苗,有其重要特点:腺病毒的某些毒株可以在禽体  相似文献   

5.
人类腺病毒载体活疫苗的开发使用近年取得重大进展。文章指明了此类疫苗的研究动向,提出了进一步发展对策,论述了应用前景,从而阐明了腺病毒是重组疫苗的重要载体。  相似文献   

6.
自从二十世纪五十年代开始认识腺病毒(Adenovirus)以来,对腺病毒的生物学和免疫学特征已经有比较多的认识。腺病毒科包括禽腺病毒属(Aviadenovius)和哺乳动物腺病毒(Mastadenov irus)两个属。除人腺病毒以外,一些哺乳动物的腺病毒和禽腺病毒也成为基因治疗和载体疫苗研究的热点,如猪腺病毒3型(PAV-3)、牛腺病毒3型(BAV-3)、绵羊腺病毒(Ovine adenovirus,OAV)、禽腺病毒(Aviadenovirus)、犬腺病毒(Canine adeno virus,CAV)和黑猩猩腺病毒(Chimpanzee adenovirus)。不同种属的腺病毒虽然基因组序列完全不同,但其结构和功能却非常相似,而且各型腺病毒之间很少有交叉免疫反应,这就为利用这些腺病毒研制基因治疗载体和活载体疫苗提供了丰富的材料。近年来的研究也发现,如果利用一种腺病毒载体来进行重复免疫,宿主针对腺病毒载体蛋白的免疫反应比较强大,造成转基因表达时间缩短,重复免疫的效果较差,换用不同的病毒载体,则可以回避这种免疫反应,提高转基因的表达时间和保护性免疫反应。腺病毒可以感染很多分裂期或静止期细胞,即使在一些高度分化的组织细胞中也可增殖,如可有效的感染肌肉组织、心、肺和脑组织,并能高效的复制、表达其基因产物,因此腺病毒成为基因治疗和活病毒载体疫苗研究的首选工具。  相似文献   

7.
2014年西非埃博拉疫情暴发后,多个埃博拉疫苗临床试验陆续开展。开展临床试验的埃博拉疫苗主要是病毒载体类疫苗,例如人腺病毒载体(Ad5和Ad26)、3型黑猩猩腺病毒载体(Ch Ad3)、水泡性口炎病毒载体(VSV)、痘病毒载体(MVA)。从免疫策略上来说,包括单次免疫与初免-加强两种免疫策略。基于Ad5、Ad26、Ch Ad3和MVA载体的埃博拉疫苗在Ⅰ、Ⅱ期临床试验中显示了良好的免疫原性,基于VSV载体的疫苗更是在Ⅲ期临床试验中显示了很好的保护性。  相似文献   

8.
重组腺病毒载体疫苗黏膜免疫机制与途径研究   总被引:1,自引:0,他引:1  
腺病毒作为载体具有许多优点,因此被广泛地应用于体外基因转导、体内接种疫苗和基因治疗等领域。近年来,国内外学者已经构建了表达不同抗原的腺病毒载体,如人(猿)免疫缺陷病毒Gag,pol,Nef,Env,狂犬病毒糖蛋白,登革热病毒包膜蛋白,乙型肝炎病毒表面抗原,丙型肝炎病毒E1、E2、core、NS3,麻疹病毒核衣壳、凝血素,呼吸道合胞病毒糖蛋白,2型单纯疱疹病毒糖蛋白B、炭疽杆菌保护性抗原等。其中有不少载体疫苗通过黏膜免疫接种,诱导机体产生具有保护作用的免疫反应。本文就重组腺病毒载体疫苗黏膜免疫机制和黏膜免疫途径的研究作一回顾。  相似文献   

9.
探讨利用腺病毒载体作为炭疽杆菌基因工程疫苗载体的可行性。从载体pcDNA3.1-PA上PCR扩增PA片断,将该片断克隆入质粒pAdTrack-CMV,得到阳性克隆pAdTrack-PA。PmeI线性化的阳性克隆转化含有腺病毒骨架质粒pAdeasy-1的BJ5183感受态细胞,经同源重组后得到重组腺病毒vAd-PA。vAd-PA经PacI线性化后,脂质体介导转染293细胞,经Western-blot检测表明PA在293细胞中得到表达。重组病毒肌肉注射免疫BALB/c小鼠,用ELISA方法检测血清中产生了特异性抗体,抗体滴度计算几何均数为1:2800。该研究为进一步研究以腺病毒为活载体的疫苗奠定了基础。  相似文献   

10.
为研制O型口蹄疫病毒(FMDV)复制缺陷型腺病毒活载体疫苗毒株,通过RT-PCR方法获得了O型FMDV的开放阅读框(ORF)基因,并定向克隆到腺病毒穿梭载体pAdTrack-CMV中,构建了重组腺病毒穿梭质粒pAdTrack-CMVORF,经PCR、酶切及测序鉴定,克隆得到的ORF编码基因序列与原始强毒株O型FMDV的ORF编码基因相似性达99.8%。将含有目的基因的穿梭质粒线性化后和腺病毒骨架载体pAdeasy-2共同电转化入大肠杆菌BJ5183感受态细胞中,得到重组腺病毒质粒pAd-ORF,经PCR和酶切鉴定正确。本研究成功获得了含有现代O型疫苗用FMDV毒株的全ORF编码基因的阳性克隆,并成功构建了含有完整编码基因表达盒的重组腺病毒穿梭质粒及其腺病毒骨架质粒。  相似文献   

11.
Herpes simplex virus (HSV) recombinants are being developed as vaccine vectors for the expression of heterologous antigens. There is concern, however, that preexisting HSV immunity may decrease their effectiveness. We have addressed this issue in an animal model. Immunized mice were inoculated with a replication-defective HSV-1 vector that expressed the Escherichia coli beta-galactosidase protein as a model antigen. We assessed vector efficacy by analyzing the immunoglobulin G (IgG) antibody response and cellular proliferative response directed against beta-galactosidase. We report that the ability of the vector to induce antibody or proliferative responses was not diminished by preexisting immunity to HSV. Of further note, the anti-HSV and anti-beta-galactosidase IgG responses following vector administration were extremely durable in both immunized and naive mice. These results indicate that the ability of a replication-defective HSV-derived vaccine vector to elicit long-lived immune responses in mice is not impaired by prior HSV exposure.  相似文献   

12.
Newcastle disease virus (NDV) is an avian virus that is being evaluated as a vaccine vector for the delivery of foreign genes in mammals. The use of NDV as a vaccine vector in these species offers two major advantages. First, NDV is highly attenuated in mammals, rendering its use inherently safe. Second, mammals lack pre-existing NDV immunity, which minimizes the risk of vaccination failure. NDV-vector vaccines are generally administered to mammals via the respiratory route. We recently showed that intramuscular vaccination with NDV-based Rift Valley fever virus (RVFV) vaccines provides complete protection in mice and induces neutralizing antibodies in sheep and cattle, the main target species of RVFV. Here, we discuss the use of NDV as a vaccine vector for applications in mammalian livestock with an emphasis on the vaccination route. We also report the results of novel experiments that underscore our notion that vaccination via a parenteral route is more effective than immunization via the respiratory route.  相似文献   

13.
A strain of Corynebacterium pseudotuberculosis, designated Toxminus, that has been rationally attenuated by deletion of the phospholipase D gene, is being developed as a live vaccine vector for the delivery of veterinary vaccine antigens. In the present study a recombinant form of the basic protease gene of the ovine footrot causative bacterium, Dichelobacter nodosus, was introduced into the vector strain using the high copy number plasmid pEP2. This strain secreted the basic protease protein. Vaccination trials in sheep with the recombinant strain demonstrated that, although an IgG immune response was elicited, the animals were not protected from footrot following artificial challenge under pen conditions. Although the sheep were not protected there was evidence that the progression of the disease was slowed.  相似文献   

14.
Because the vaccine vectors currently being evaluated in human populations all have significant limitations in their immunogenicity, novel vaccine strategies are needed for the elicitation of cell-mediated immunity. The nonpathogenic, rapidly growing mycobacterium Mycobacterium smegmatis was engineered as a vector expressing full-length human immunodeficiency virus type 1 (HIV-1) HXBc2 envelope protein. Immunization of mice with recombinant M. smegmatis led to the expansion of major histocompatibility complex class I-restricted HIV-1 epitope-specific CD8(+) T cells that were cytolytic and secreted gamma interferon. Effector and memory T lymphocytes were elicited, and repeated immunization generated a stable central memory pool of virus-specific cells. Importantly, preexisting immunity to Mycobacterium bovis BCG had only a marginal effect on the immunogenicity of recombinant M. smegmatis. This mycobacterium may therefore be a useful vaccine vector.  相似文献   

15.
Bovine parainfluenza virus type 3 (bPIV3) is being evaluated as an intranasal vaccine for protection against human PIV3 (hPIV3). In young infants, the bPIV3 vaccine appears to be infectious, attenuated, immunogenic, and genetically stable, which are desirable characteristics for an RNA virus vector. To test the potential of the bPIV3 vaccine strain as a vector, an infectious DNA clone of bPIV3 was assembled and recombinant bPIV3 (r-bPIV3) was rescued. r-bPIV3 displayed a temperature-sensitive phenotype for growth in tissue culture at 39 degrees C and was attenuated in the lungs of Syrian golden hamsters. In order to test whether r-bPIV3 could serve as a vector, the fusion and hemagglutinin-neuraminidase genes of bPIV3 were replaced with those of hPIV3. The resulting bovine/human PIV3 was temperature sensitive for growth in Vero cells at 37 degrees C. The replication of bovine/human PIV3 was also restricted in the lungs of hamsters, albeit not as severely as was observed for r-bPIV3. Despite the attenuation phenotypes observed for r-bPIV3 and bovine/human PIV3, both of these viruses protected hamsters completely upon challenge with hPIV3. In summary, bPIV3 was shown to function as a virus vector that may be especially suitable for vaccination of infants and children against PIV3 and other viruses.  相似文献   

16.
昆虫杆状病毒表达载体系统在疫苗研究中的应用进展   总被引:1,自引:0,他引:1  
昆虫杆状病毒表达载体系统(Baculovirus expression vector system,BEVS)已成功应用于多种蛋白的表达,并为疫苗开发提供了充足的原材料。相比其他表达系统,BEVS具有许多优势:杆状病毒专一寄生于无脊椎动物,安全性高;重组蛋白表达水平高;可对重组蛋白进行正确折叠和翻译后修饰,获得具有生物活性的蛋白;适应于多基因表达如病毒样颗粒(Virus-like particle)的复杂设计;适用于大规模无血清培养等。为了更好地理解BEVS在疫苗研究中的应用前景,文中将从BEVS的发展及其在疫苗研究中的应用等方面进行综述。  相似文献   

17.
2019年底于中国武汉暴发的新型冠状病毒肺炎疫情来势凶猛,迅速蔓延全球,并被世界卫生组织列为“国际关注的突发公共卫生事件”,给全人类的健康及经济发展造成难以估量的损害。新型冠状病毒对人群普遍易感且传染性强,在无特效药物及治疗手段的情况下,疫苗接种是防控COVID-19疫情最有效且最经济的途径。目前全球疫苗研发正在加速进行,各国之间通力合作,共同应对此次疫情。主要对目前正在研发的针对SARS-CoV-2的灭活疫苗、病毒载体疫苗、基因工程重组亚单位疫苗、核酸疫苗的研究进展进行综述。  相似文献   

18.
Shata MT  Hone DM 《Journal of virology》2001,75(20):9665-9670
A prototype Shigella human immunodeficiency virus type 1 (HIV-1) gp120 DNA vaccine vector was constructed and evaluated for immunogenicity in a murine model. For comparative purposes, mice were also vaccinated with a vaccinia virus-env (vaccinia-env) vector or the gp120 DNA vaccine alone. Enumeration of the CD8(+)-T-cell responses to gp120 after vaccination using a gamma interferon enzyme-linked spot assay revealed that a single intranasal dose of the Shigella HIV-1 gp120 DNA vaccine vector elicited a CD8(+) T-cell response to gp120, the magnitude of which was comparable to the sizes of the analogous responses to gp120 that developed in mice vaccinated intraperitoneally with the vaccinia-env vector or intramuscularly with the gp120 DNA vaccine. In addition, a single dose of the Shigella gp120 DNA vaccine vector afforded significant protection against a vaccinia-env challenge. Moreover, the number of vaccinia-env PFU recovered in mice vaccinated intranasally with the Shigella vector was about fivefold less than the number recovered from mice vaccinated intramuscularly with the gp120 DNA vaccine. Since the Shigella vector did not express detectable levels of gp120, this report confirms that Shigella vectors are capable of delivering passenger DNA vaccines to host cells and inducing robust CD8(+) T-cell responses to antigens expressed by the DNA vaccines. Furthermore, to our knowledge, this is the first documentation of antiviral protective immunity following vaccination with a live Shigella DNA vaccine vector.  相似文献   

19.
Vesicular stomatitis virus (VSV) is a highly cytopathic virus being developed as a vaccine vector due to its ability to induce strong protective T cell and antibody responses after a single dose. However, little is known regarding the mechanisms underlying the potent immune responses elicited by VSV. We previously generated a VSV vector expressing the hepatitis B virus middle envelope surface glycoprotein (MS) that induces strong MS-specific T cell and antibody responses in mice. After synthesis in the cytoplasm, the MS protein translocates to the endoplasmic reticulum, where it forms subviral particles that are secreted from the cell. To better understand the contributions of secreted and intracellular protein to the VSV-induced immune response, we produced a vector expressing a secretion-deficient MS mutant (MS(C69A)) and compared the immunogenicity of this vector to that of the wild-type VSV-MS vector in mice. As expected, the MS(C69A) protein was not secreted from VSV-infected cells and displayed enhanced proteasome-mediated degradation. Surprisingly, despite these differences in intracellular protein processing, the T cell and antibody responses generated to MS(C69A) were comparable to those elicited by virus expressing wild-type MS protein. Therefore, when it is expressed from VSV, the immune responses to MS are independent of particulate antigen secretion and the turnover rate of cytoplasmic protein. These results are consistent with a model in which the immune responses to VSV are strongly influenced by the replication cycle of the vector and demonstrate that characteristics of the vector have the capacity to affect vaccine efficacy more than do the properties of the antigen itself.  相似文献   

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