腮腺炎疫苗免疫效果研究进展

目前广泛使用的腮腺炎减毒活疫苗株有Jeryl Lynn株、Leningrad-3株以及它们的衍生株.疫苗的免疫效果为80%-100%,差异较其他同类疫苗大,可能的原因首先是这些病毒株是几个亚株形成的混合物.在某些疫苗生产用细胞上连续传代,亚株的比例会出现变化;但最近发现,人类HLA和免疫调节相关细胞因子及其受体基因多样性对腮腺炎疫苗接种效果有重要影响;有可能是以上两者结合导致了现阶段腮腺炎免疫效果的较大差异,而后者也许是更主要的原因.2004年以来,英国、美国和西班牙均发生了疫苗接种人群中的腮腺炎流行,疫苗的保护效果随时间而减弱是其主要原因.目前仍应遵照WHO的建议,提供及时的追加免疫机会以维持人群的免疫水平.     

腮腺炎疫苗免疫效果研究进展

目前广泛使用的腮腺炎减毒活疫苗株有Jeryl Lynn株、Leningrad-3株以及它们的衍生株.疫苗的免疫效果为80%-100%,差异较其他同类疫苗大,可能的原因首先是这些病毒株是几个亚株形成的混合物.在某些疫苗生产用细胞上连续传代,亚株的比例会出现变化;但最近发现,人类HLA和免疫调节相关细胞因子及其受体基因多样性对腮腺炎疫苗接种效果有重要影响;有可能是以上两者结合导致了现阶段腮腺炎免疫效果的较大差异,而后者也许是更主要的原因.2004年以来,英国、美国和西班牙均发生了疫苗接种人群中的腮腺炎流行,疫苗的保护效果随时间而减弱是其主要原因.目前仍应遵照WHO的建议,提供及时的追加免疫机会以维持人群的免疫水平.     

流行性腮腺炎的流行现状及疫苗免疫策略

流行性腮腺炎(腮腺炎)是由腮腺炎病毒(mumps virus,MuV)导致的急性全身性传染病,接种疫苗是预防MuV感染最有效的手段.腮腺炎疫苗广泛应用后,全球腮腺炎发病率大幅下降,但近些年却多次发生小规模腮腺炎暴发,可能的原因主要包括:疫苗接种覆盖率不够高、疫苗效果不理想、人群免疫力下降和流行株基因型改变.针对这些情况,应调整免疫接种策略,并需研发新疫苗.     

腮腺炎病毒的基因分型及当前疫苗的免疫效果

腮腺炎是由腮腺炎病毒所导致的急性全身性传染病。腮腺炎病毒只有一个血清型，目前基于其SH基因序列的差异可以区分出A～K 11个基因型。一般使用聚合酶链反应(PCR)与逆转录酶(RT)-PCR分子生物学方法来研究病毒的基因。不同疫苗株的免疫效果有区别，1剂接种与2剂接种的效果也在监测中。已初步建立动物模型可供病毒致神经毒性研究。有报道认为病毒基因型之间存在抗原性差异，但病毒各基因型间有交叉保护作用存在，所以目前使用的疫苗都是安全、有效的。     

腮腺炎病毒的基因分型及当前疫苗的免疫效果

腮腺炎是由腮腺炎病毒所导致的急性全身性传染病。腮腺炎病毒只有一个血清型,目前基于其SH基因序列的差异可以区分出A～K 11个基因型。一般使用聚合酶链反应(PCR)与逆转录酶(RT) - PCR分子生物学方法来研究病毒的基因。不同疫苗株的免疫效果有区别,1剂接种与2剂接种的效果也在监测中。已初步建立动物模型可供病毒致神经毒性研究。有报道认为病毒基因型之间存在抗原性差异,但病毒各基因型间有交叉保护作用存在,所以目前使用的疫苗都是安全、有效的     

WHO关于腮腺炎疫苗的意见书

本文介绍了腮腺炎的病原学、各种腮腺炎疫苗的免疫程序、效果、不良反应以及WHO对腮腺炎疫苗的意见.     

腮腺炎疫苗的现状

腮腺炎疫苗为减毒活疫羁。接种后的主要问题是Ｕｒａｂｅ株疫苗可引起脑膜炎，大多数国家现已选用Ｊｅｒｙ１Ｌｙｎｎ株疫苗。目前研究的重点是病毒基因疗列分析，此法有助于疫苗株与野毒株鉴别，腮腺炎流行病学研究和疫苗的质量控制。     

腮腺炎病毒及疫苗研究进展

随着对腮腺炎病毒研究的深入,人们对腮腺炎病毒的基因组结构、病毒蛋白的结构和功能有了更多的认识,病毒表面的两种糖蛋白——血凝素-神经氨酸酶(HN)蛋白和融合(F)蛋白是重要的抗原决定簇,HN蛋白抗体可中和病毒感染,而F蛋白是溶血抗原。现今使用的腮腺炎疫苗为减毒活疫苗,对病毒基因序列分析后发现接种疫苗后出现的脑膜炎病例主要与Urabe株有关,目前正在探索发展新一代腮腺炎疫苗。     

腮腺炎病毒及凤苗研究进展

随着对腮腺炎病毒研究的深入，人们对腮腺炎病毒的基因组结构、病毒蛋白的结构和功能有了更多的认识，病毒表面的两种糖蛋白－－血凝素－神经氨酸酶（ＨＮ）蛋白和融合（Ｆ）蛋白是重要的抗原决定簇，ＨＮ蛋白抗体可中和病毒感染，而Ｆ蛋白是溶血抗原。现今使用的腮腺炎疫苗为减毒活性疫苗，地病毒基因序列分析后发现接种疫苗后出现的脑膜炎病例主要与Ｕｒａｂｅ株有关，目前正在探索发展新一代腮腺炎疫苗。     

加强流动儿童计划免疫与腮腺炎及并发症的预防

腮腺炎是一种传染性很强、急性发作的儿童时期的一种传染性疾病。流行性腮腺炎病毒对腺体及神经组织有较强的亲和力,因此除腮腺炎外,尚可并发睾丸炎、卵巢炎、乳腺炎、心肌炎及脑膜炎等病症。近年来流动人口腮腺炎发病率有逐年上升的趋势,应加强流动儿童计划免疫工作,预防和控制流行性腮腺炎的发生。1腮腺炎特点及目前流行状况流行性腮腺炎是腮腺炎病毒所引起的小儿急性传染病,临床以腮腺肿大和疼痛伴有发热为其主要特征。主要是通过呼吸道飞沫传染,所以属于呼吸道传染病,多发生于学龄前及学龄期儿童[1]。传染性较强,在儿童集体中易引起流行,有时可以使全班儿童发病。目前,已有预防疫苗,只要做好预防接种工作,流行性腮腺炎是可以避免发生的;近年我们在临床实践中发现患流行性腮腺炎的儿童多为流动人口,因为其流动的特性而不能及时接受儿童计划免疫管理,家长缺乏儿童计划免疫预防接种的常识,使儿童不能及时有效接种腮腺炎疫苗而发病,这种疾病虽然不致于引起孩子的生命危险,但可以并发一些合并症,其后果要比原发病腮腺炎要严重,家长、医生对此应引起必要的注意。2腮腺炎合并症2.1合并性腺炎症孩子得了腮腺炎,家长关心孩子将来的生育问题。确实,腮腺炎可以并发睾丸炎或卵巢炎...     

Aseptic meningitis following mumps vaccine. A retrospective survey by the French Regional Pharmacovigilance centres and by Pasteur-Mérieux Sérums & Vaccins

Since 1989 many case series and observational studies of aseptic meningitis (AM) associated with the use of live attenuated mumps vaccines containing the Urabe AM9 strain have been reported worldwide. The aim of this retrospective reported AM in France following mumps vaccination with monovalent or multivalent vaccines containing the Urabe strain. Fifty-four cases of AM were reported to the Regional Pharmacovigilance centres or to the manufacturer from the time each vaccine was launched up until June 1992. Twenty cases were temporally associated with the administration of a monovalent mumps vaccine and 34 with a trivalent measles, mumps and rubella vaccine (MMR). A mumps virus was isolated in four cases in the cerebrospinal fluid and an Urabe-like strain was characterized twice by polymerase chain reaction (PCR). A probable mumps origin was assumed in 17 other cases where the patients presented with other clinical or biological signs of mumps infection. The clinical outcome of AM, known in 87% of the population, was always favourable. The global incidence of mumps vaccine-associated AM was 0.82/100,000 doses, which is significantly lower than the incidence in the unvaccinated population. Even considering that the actual incidence of AM is much higher when assessed by active surveillance studies, the risk/benefit ratio of mumps vaccine remains in favour of vaccination.     

麻疹、腮腺炎、风疹、水痘联合减毒活疫苗的生产工艺研究

目的  建立麻疹、腮腺炎、风疹、水痘联合减毒活疫苗（combined live attenuated measles，mumps，rubella and varicella vaccine，MMRV）的生产工艺。方法  根据现有疫苗病毒原液生产工艺，将麻疹病毒沪-191纯化株、腮腺炎病毒S79株、风疹病毒BRD-Ⅱ株和水痘-带状疱疹病毒Oka株在原代鸡胚成纤维细胞或人二倍体细胞MRC-5株中制备高滴度病毒原液，并超低温保存。筛选无明胶冻干稳定剂配方。按国外已上市同类产品的病毒配比，研究MMRV中4种病毒的原液配制滴度及成品配制比例，建立最佳冻干工艺。结果  用筛选出的适合于MMRV的无明胶冻干稳定剂配方进行试验，确定病毒原液的配制滴度为，麻疹4.6 lg半数细胞培养感染量（50% cell culture infective dose，CCID₅₀）/ml、腮腺炎5.8 lgCCID₅₀/ml、风疹4.3 lgCCID₅₀/ml、水痘4.8 lg噬斑形成单位（plaque forming unit，PFU）/ml。使成品中腮腺炎病毒滴度至少达到麻疹和风疹和水痘病毒的10倍，水痘病毒滴度高于现有单价水痘疫苗。连续制备3批MMRV，平均病毒滴度为，麻疹4.5 lgCCID₅₀/ml、腮腺炎5.1 lgCCID₅₀/ml、风疹4.3 lgCCID₅₀/ml、水痘4.6 lgPFU/ml；平均水分为1.2%。其他项目检定均合格。结论  建立了MMRV的生产工艺，可以稳定生产出达到国外同类产品质量标准并符合我国4种单价减毒活疫苗国家标准的产品。     

腮腺炎病毒在转瓶和细胞工厂中制备的比较

目的 比较15 L转瓶及40层细胞工厂工艺制备腮腺炎减毒活疫苗的病变情况、病毒滴度和原液各项质量指标。方法 分别采用15 L转瓶及40层细胞工厂培养原代鸡胚细胞1～3 d后感染S79株腮腺炎病毒,继续培养至5～7 d收获病毒液。两种培养方式收获的腮腺炎病毒单次收获液分别合并后获得疫苗原液,并进行相关检定。结果 转瓶收获的单次病毒液0和21 d检定的平均滴度分别为6.6、6.1 lg半数细胞培养感染量（50% cell culture infective dose,CCID₅₀）/ml。细胞工厂收获的单次病毒液0和21 d检定的平均滴度分别为6.8、6.2 lgCCID₅₀/ml。两种方式制备的腮腺炎减毒活疫苗原液各项质量指标均合格。结论 应用40层细胞工厂工艺制备腮腺炎减毒活疫苗的细胞病变情况及单次病毒收获液滴度均优于15 L转瓶培养工艺,此实验为40层细胞工厂制备腮腺炎减毒活疫苗的大规模生产及工艺改进奠定了基础。     

基于杆状病毒表达系统的流感病毒样颗粒疫苗研究进展

流感疫苗是目前应对流感最有效的措施,传统疫苗包括全病毒灭活疫苗、裂解疫苗和减毒活疫苗,近年来逐渐成为研发趋势的有重组亚单位疫苗、核酸疫苗、活病毒载体疫苗等。病毒样颗粒(virus-like particle,VLP)疫苗作为特殊形式的亚单位疫苗,具有生产迅速、安全性高、免疫原性较高等优势。VLP可以高效地诱发体液免疫与细胞免疫,且可经多种途径接种。目前已有多种表达系统用于制备VLP,其中应用最为广泛的是杆状病毒表达系统。此文综述了流感病毒VLP的类型、组装、抗原选择、免疫途径以及流感病毒VLP疫苗在杆状病毒表达系统中的研究进展。     

水痘减毒活疫苗无明胶稳定剂的筛选和应用

 目的   研制不含明胶的新型稳定剂,以提高水痘减毒活疫苗的安全性。方法   以现行水痘减毒活疫苗稳定剂配方为基础,去除明胶,配制4种不同的新型稳定剂（B、C、D、E配方）。用无明胶稳定剂制备水痘减毒活疫苗,并将制备的无明胶稳定剂疫苗（B、C、D、E疫苗）与现行的含明胶稳定剂疫苗（作为对照的A疫苗）进行比较,确定最佳稳定剂配方。结果   疫苗成品于37 ℃放置7 d后,A、B、C、D、E疫苗的相关质量指标均符合《水痘减毒活疫苗注册标准》的要求,病毒滴度分别为3.6、3.5、3.3、3.3、3.3 lg PFU/0.5 ml,但C、D、E疫苗的病毒滴度已降至临界值。疫苗成品于2~8 ℃放置24个月后,A、B、C、D、E疫苗的病毒滴度分别为3.4、3.4、3.2、3.0、2.8 lg PFU/0.5 ml,其中C、D、E疫苗的病毒滴度已低于规定的标准（3.3 lg PFU/0.5 ml）,仅B疫苗的相关质量标准符合规定的要求,且与A疫苗（对照）没有差异。 结论   去除明胶的B配方稳定剂对水痘病毒有较好的保护作用。     

病毒性疫苗渗透压摩尔浓度的质量控制

目的  通过检测6种病毒性疫苗成品的渗透压摩尔浓度,比较不同疫苗检测均值的差异,并观察同种疫苗检测值的批间稳定性,为增加病毒性疫苗质量控制手段提供依据。方法  采用冰点下降法检测麻疹减毒活疫苗、风疹减毒活疫苗、麻疹腮腺炎联合减毒活疫苗、麻疹腮腺炎风疹联合减毒活疫苗、水痘减毒活疫苗、流感病毒裂解疫苗的渗透压摩尔浓度,对检测值进行统计学处理,计算变异系数。以麻疹腮腺炎风疹联合减毒活疫苗的渗透压摩尔浓度检测均值作为对照,进行方差齐性检验及假设检验,比较各疫苗检测均值的差异。结果  麻疹腮腺炎联合减毒活疫苗与对照相比,均值差异无统计学意义（t=1.66,P>0.05）;麻疹减毒活疫苗、风疹减毒活疫苗、水痘减毒活疫苗及流感病毒裂解疫苗与对照相比,均值差异均有统计学意义（Z>1.96,P<0.001）。同种疫苗批间渗透压摩尔浓度较为稳定,变异系数均<3%,变化幅度能控制在90%~110%均值范围内。结论  6种病毒性疫苗渗透压摩尔浓度存在一定差异,但同种疫苗检测值批间稳定性较好,因此,应根据不同疫苗的渗透压摩尔浓度,分别制定质量控制标准。     

Measles,mumps, rubella vaccine (Priorix; GSK-MMR): a review of its use in the prevention of measles,mumps and rubella

GSK-MMR (Priorix) is a trivalent live attenuated measles, mumps and rubella (MMR) vaccine which contains the Schwarz measles, the RIT 4385 mumps (derived from the Jeryl Lynn mumps strain) and the Wistar RA 27/3 rubella strains. GSK-MMR as a primary vaccination demonstrated high immunogenicity in clinical trials in >7500 infants aged 9-27 months, and was as immunogenic as Merck-MMR (MMR II). However, antimumps seroconversion rates and geometric mean titres (GMTs) were significantly higher in infants receiving GSK-MMR compared with Berna-MMR (Triviraten trade mark ) recipients. Coadministration of GSK-MMR with a varicella vaccine (Varilrix; GSK-MMR/V) did not significantly affect the immunogenicity of GSK-MMR. A persistent immune response to GSK-MMR has been demonstrated in follow-up data from several randomised trials. GMTs for measles, mumps and rubella antibodies remained high in GSK-MMR recipients 1-2 years post-vaccination and were similar to those in Merck-MMR recipients. The immunogenicity of GSK-MMR was high, and similar to that of Merck-MMR, when used as a second dose in children aged 4-6 or 11-12 years who had received a primary vaccination with Merck-MMR in their second year of life. Although there are no protective efficacy data concerning the GSK-MMR vaccine to date, the rubella Wistar RA 27/3 rubella and Schwarz measles strains have well established protective efficacy; the new RIT 4385 mumps strain is expected to afford similar protection from mumps to that achieved with mumps vaccines that contain the Jeryl Lynn mumps strain (e.g. Merck-MMR). GSK-MMR was well tolerated as a primary or secondary vaccination, and in most clinical studies comparing GSK-MMR with Merck-MMR as a primary vaccination in infants, GSK-MMR was associated with significantly fewer local adverse events (e.g. pain, swelling and redness). The incidence of local adverse events with GSK-MMR, GSK-MMR/V or Berna-MMR was similar. GSK-MMR and Merck-MMR were associated with similar rates of fever, rash and parotid gland swelling, but Berna-MMR was associated with a lower incidence of fever. In conclusion, GSK-MMR is a highly immunogenic MMR vaccine with good tolerability. In clinical trials, the immunogenicity of GSK-MMR was similar to that of Merck-MMR, and the mumps component was more effective at eliciting seroprotection than that of Berna-MMR. Furthermore, GSK-MMR causes fewer injection-site adverse events than Merck-MMR. As such, GSK-MMR is an attractive alternative for immunisation against measles, mumps and rubella.     

Current status and potential application of ISCOMs in veterinary medicine

The immune stimulating complex (ISCOM) is a 40 nm nanoparticle used as a delivery system for vaccine antigens, targeting the immune system both after parenteral and mucosal administration. The ISCOM is made up of saponin, lipids and antigen usually held together by hydrophobic interaction between these three components. The compulsory elements to form the ISCOM structure are cholesterol and saponin. When the antigen is omitted the ISCOM-MATRIX is formed. There are a number of saponins that can form ISCOMs, and many other substances (including antigens, targeting and immuno-modulating molecules) can be incorporated into the ISCOM provided they are hydrophobic or rendered to be hydrophobic. Thus, it is possible to create ISCOM particles with different properties. After parenteral immunisation of the ISCOM, the T cell response is first detected in the draining lymph node. Subsequently, the T cell response is localised to the spleen, while the B cell response is first found both in the draining lymph nodes and in the spleen. Up to 50 days later, the majority of the antibody producing cells is found in the bone marrow (BM). In contrast, antigens that have been adjuvanted in an oil emulsion, limit the T cell response to the draining lymph nodes while the B cell response is found in the draining lymph nodes and spleen, but not in the BM. The ISCOM efficiently evokes CD8+, MHC class 1 restricted T cell response. The deposit of antigens both to the endosomal vesicles and to the cytosol of antigen presenting cells (APCs) explains why both T helper cells (vesicles) and cytotoxic T lymphocytes (cytosol) are efficiently induced by ISCOMs. The T helper (Th) cell response is balanced in the sense that both Th1 and Th2 cells are induced. Prominent IL-12 production by cells in the innate system is a characteristic reaction induced by ISCOMs, promoting the development of a strong Th1 response. After mucosal administration by the intranasal or the intestinal routes, the ISCOM induces strong specific mucosal IgA responses in local and remote mucosal surfaces. Also T cell responses are evoked by the mucosal administration. A large number of experimental ISCOM vaccines have been tested and protection has been induced against a number of pathogens in various species including chronic and persistent infections exemplified by human immune deficiency virus 1 (HIV-1), and 2 (HIV-2) and simian immune deficiency virus (SIV) in primates, and various herpes virus infections in several species. In contrast to a conventional rabies virus vaccine the ISCOM rabies formulation protected mice after exposure to the virulent virus. Recently, experimental ISCOM vaccines were shown to efficiently induce immune response in newborns of murine and bovine species in the presence of maternal antibodies, while conventional vaccines have failed. ISCOM vaccines are on the market for horses and cattle and several other ISCOM vaccines are under development. Since the ISCOM and the ISCOM-MATRIX can be blended with live attenuated vaccine antigens without hampering the proliferation of the live vaccine antigens, it opens the possibility to use the ISCOM adjuvant system in a mixture of live and killed vaccine antigens.