伤寒Vi多糖菌苗人群免疫效果评价

１９９５年和１９９７年,广西合浦县公馆镇部分地区曾两次发生伤寒副伤寒流行,为尽快控制疫情,我们除了做好疫区食品卫生和水源防护、净化、消毒等工作外,还对易感人群进行了伤寒Ｖｉ多糖菌苗预防注射,现将两年跟踪观察的结果报告如下。１对象与方法１．１对象选择暴...     

伤寒Vi多糖疫苗在我国的研究与应用现状

伤寒是严重影响我国人民健康的常见肠道传染病,研究和使用疫苗无疑是预防伤寒的有效手段。伤寒Vi多糖疫苗是一种目前被国内外公认为安全、有效的疫苗,并被WHO推荐使用。本文就我国在伤寒Vi多糖疫苗的稳定性、安全性与免疫效果等方面的研究与应用现状进行综述。     

伤寒Vi多糖菌苗免疫效果观察

伤寒—副伤寒甲乙三联菌苗 (ＴＡＢ)因需免疫三次 ,且接种反应重 ,往往不能完成全程免疫而影响其效果。 90年代初期研制的伤寒Ｖｉ多糖菌苗只需注射一针 ,接种反应少 ,保护率达到71 3 5 %[1] ,是目前公认的理想疫苗。关于该疫苗免疫学效果 ,国内报道不多。 1998年 9月 ,本地区下陈镇伤寒暴发 ,我们对疫区易感人群应急接种伤寒Ｖｉ多糖菌苗 ,并对免疫效果进行观察 ,现将结果报告如下。1　对象与方法1 1　对象　伤寒接触者、饮食服务人员、水厂工作人员、幼儿和中小学生及企业职工 ,接种 65 2 5人。随机选择其中部分中学生和企业职工 194人 …     

伤寒Vi多糖菌苗免疫效果及持久性研究

伤寒是我国法定乙类传染病.1990～1998年我省伤寒发病率为0.55/10万至4.39/10万,并在局部地区及特种人群中发生多起暴发或流行,因而控制及降低伤寒病的发病率,仍是一项重要任务.过去使用的伤寒老三联菌苗(TAB),免疫效果虽好,但注射局部及全身反应重,免疫接种时间较长(初次免疫程序为3次肌注),全程免疫要一个月完成,难以保证全程免疫,常常出现所谓“3、2、1现象”,故影响推广使用,更达不到预期的免疫效果.我国于1990年已经成功地研制出“伤寒Vi多糖菌苗”,并进行了批量生产.     

伤寒 Vi多糖菌苗的研究现状

伤寒是由伤寒杆菌引起的急性肠道传染病 ,它至今仍然是许多发展中国家发病率较高的传染病 ,据估计伤寒在全世界每年约有１６００万人次发病 ,死亡约６０万人［１］。因此伤寒仍是很多发展中国家重要的公共卫生问题之一。１伤寒菌苗研究史自１９世纪末德国的Ｐｆｅｉｆｆｅｒ和Ｋｏｌｌｅ首次应用伤寒菌体菌苗预防伤寒以来 ,至今已有１００年的历史 ,在此期间各国先后研究出１０余种伤寒菌苗。我国自５０年代以来在易感人群中使用的伤寒菌体菌苗 ,为每ｍｌ含５亿个菌 ,其中伤寒杆菌２．５亿个 ,副伤寒甲、乙各１．２５亿个 ,采用皮下注射３次…     

国产与法国Merieux产伤寒Vi多糖菌苗免疫持久性观察

为了解国产伤寒Ｖｉ菌苗和法国菌苗的免疫持久性大于１９９５年在江苏省某中学１２￣１６岁学生中进行血清学观察。结果表明，免后１个月血清Ｖｉ抗体滴度明显上升，国产菌苗和法国菌苗抗体的ＧＭＴ分别为３６．９４和３５．４９，四倍增长率分别为９１．８０％和８９．６６％，免后６个月Ｖｉ抗体的ＧＭＴ分别为１５．３８和１５．８０，四倍增长率分别为６１．２２％和５９．０９％，免后１２个月Ｖｉ抗体的ＧＭＴ分别为１５．３８     

伤寒Vi多糖菌苗免疫后长期效果观察

目的研究伤寒Vi多糖菌苗免疫后长期效果。方法现场实验流行病学。结果接种后伤寒Vi多糖菌苗1~3年的有一定的保护作用,且在这3年中保护效果无差别。结论接种伤寒Vi多糖菌苗是今后预防伤寒的重要措施之一,但不必要每年均接种。     

伤寒Vi多糖菌苗免疫效果观察

通过对１５０名学生接种伤寒Ｖｉ多糖菌苗后３年追踪观察表明：接种伤寒Ｖｉ多糖菌苗后体内可快速产生Ｖｉ抗体，免后１月抗体阳性率为９７．３％，ＧＭＴ为３８．３４，且Ｖｉ抗体在体内至少可维持２年以上的较高水平；免后３年加强１针，Ｖｉ体内至少可维持２年以上的较高水平；阳性率为８３．３％，ＧＭＴ为２５，２０，但没有达到初免后１月水平。结合伤寒Ｖｉ多糖菌苗流行病学观察资料，说明伤寒Ｖｉ多糖菌苗接种后人体至少有２     

伤寒Vi多糖菌苗流行病学效果

本文对我国伤寒Ｖｉ多糖菌苗研制协作组制备的伤寒Ｖｉ多糖菌苗进行接种反应及流行病学效果观察，并以其稀释液作为对照，对７７７名接种者的反应观察结果表明，菌苗组发热轻、中反应率分别为１６．９３％和０．０５％，对照组分别为１５．０１％和０．０３％，两者发热反应率无显著差异。菌苗组仅出现两例局部轻反应。对８１５０６名接种者的流行病学观察，以血培养伤寒杆菌阳性作为病人诊断标准，菌苗的保护指数为３．４９，保护率为７１．３５％，总的保护指数为４．５８，保护率为７８．１７％。临床资料显示，接种组发病者的发热强度明显低于对照组发病者。笔者认为伤寒Ｖｉ多糖菌苗全身、局部反应轻微，安全性好，保护率较高，发病者可降低发热强度，且初免只需注射一针，是一种值得推广使用的新一代菌苗     

糖尿病患者接种伤寒Vi多糖疫苗发生过敏性皮疹1例报告

2006—07—03，贵州省遵义县疾病预防控制中心某职工，因接种伤寒Vi多糖疫苗发生过敏性皮疹，经治疗痊愈。     

伤寒Vi多糖菌苗流行病学效果观察

对我国研制的伤寒Vi多糖菌苗进行接种反应及流行病学效果观察，并以其稀释液作为对照，对777名接种者的反应观察结果表明，菌苗组发热弱、中反应率分别为16．93％和0．05％，对照组分别为15．01％和0．03％．两者发热反应率无显著差异。菌苗组仅出现2例局部轻反应。对81506名接种者观察，以血培养伤寒杆菌阳性作为病人诊断标准，菌苗的保护指数为3．49，保护率为71．35％。临床资料显示，接种组发病者的发热强度明显低于对照组发病者。作者认为该苗全身、局部反应轻微，安全性好，保护率较高，发病者可降低发热强度，且初免只需注射一针，是一种值得推广使用的新一代菌苗。     

5～60岁人群伤寒Vi多糖疫苗和A群脑膜炎球菌多糖疫苗大规模接种结果分析

为考核国产伤寒Vi多糖疫苗在现场试验的效果 ,以A群脑膜炎球菌多糖疫苗为对照 ,对广西壮族自治区河池市城市和农村的 5～ 6 0岁居民进行了一次大规模接种。结果显示 :应接种对象 1180 71人 ,实际接种 92 4 76人 ,接种率为 78 32 % ,其中伤寒Vi多糖疫苗为 76 87% ,A群脑膜炎球菌多糖疫苗为 79 6 9% ;接种率最高的组群接种率为 92 4 8% ,最低为 6 5 2 0 %。按城乡划分 ,城区的接种率为 77 2 9% ,农村的接种率为 80 5 8% ,组群接种率的高低分布无明显的地理性差异。 5～ 9岁接种率最高为 89 6 5 % ,2 0～ 2 9岁接种率最低为 6 9 0 7% ;男女接种率分别为79 0 7%和 82 11%。有 6 6人被观察到或报告出现不良反应 ,不良反应发生率为 71 37/ 10万。表明两种疫苗的安全性好。在大规模疫苗接种中 ,充分发挥当地干部的宣传组织作用 ,并把接种的有关信息提前通知当地居民 ,对于提高接种率十分重要。补漏接种能使接种率低的组群得到显著的提高。在大规模疫苗接种中必须严格遵守安全注射操作程序 ,避免发生不安全注射事故。两种疫苗的平均接种率、年龄别接种率、性别接种率、组群接种率的地理分布均达到了较好均衡性 ,是可比的 ,为今后考核疫苗效果提供了良好的现场背景     

Duration of Vi antibodies in participants vaccinated with Typhim Vi (Typhoid Vi polysaccharide vaccine) in an area not endemic for typhoid fever

After a single injection of Typhim Vi^® (typhoid Vi polysaccharide vaccine), serum antibody concentrations were monitored for 3 years in 37 adults who resided where typhoid fever was not endemic. Anti-Vi antibody concentrations declined progressively during the study, to levels that support the current US recommendation for revaccination every 2 years.     

组群随机试验在伤寒疫苗效果观察中的应用研究

目的用组群随机试验实现伤寒Vi疫苗效果观察的研究设计和实施应用。方法采用组群随机试验方法确定试验组和对照组所需样本量，并组织实施大规模疫苗接种，在试验组接种伤寒Vi疫苗、对照组接种流脑疫苗。结果根据组群随机试验方法计算共需要观察对象为96121人，分为108个组群。根据组群大小、地理位置(城乡)及性质(学校、机关、厂矿、人口特征)分层配对，确定试验组分为53个组群共44054人，对照组为54个组群共48422人。对两组间各主要混杂因子(年龄、性别、居住地点、主要人群的经济收入、受教育程度、主要职业)等进行分析，发现两组之间总体相差不大，具有较好的均衡性与可比性。结论组群随机抽样法应用于大规模疫苗效果观察试验，能较好地控制组间混杂因子，使干预的实际效果得到科学的评价；实施也比较简单，被干预对象容易接受，可行性高。     

A novel method for purification of Vi capsular polysaccharide produced by Salmonella enterica subspecies enterica serovar Typhi

Vi capsular polysaccharide is the major component of Vi polysaccharide typhoid vaccines. Vi is synthesized during growth of Salmonella enterica subspecies enterica serovar Typhi and is released into the fermentation broth in large quantities. Along with the Vi considerable amounts of impurities consisting of bacterial protein, nucleic acid and lipopolysaccharide (LPS) as well as media components contaminate the fermentation broth. A purification method based on selective precipitation of Vi using the cationic detergent cetavlon was developed to separate impurities from Vi. A novel method for handling the Vi precipitate using 0.2 μm sterilizing grade filters to trap and wash the Vi and then, after re-solubilization, allow the Vi to pass through the filter was developed. Cetavlon selectively precipitates Vi and is the major purification step in the process, however, the conditions must be carefully controlled otherwise LPS will co-precipitate in large quantities. Various diafiltration steps help to remove contaminating protein, nucleic acid and fermentation media components as well as chemicals added during the process to induce precipitation of either Vi or contaminants. The final yield of purified Vi was approximately 45% and the bulk concentrate complied with the specifications defined in the WHO recommendations for Vi polysaccharide vaccine. Analysis of the Vi by size exclusion chromatography revealed a uniform peak with a narrow size distribution. The Nuclear Magnetic Resonance spectrum was similar to Vi produced by other methods. The method developed produces large quantities of Vi using low cost production methods translating into Vi based vaccines that can be produced at affordable prices for use in developing countries.     

Preparation and testing of a Vi conjugate vaccine using pneumococcal surface protein A (PspA) from Streptococcus pneumoniae as the carrier protein

In the current study pneumococcal surface protein A (PspA) was conjugated to Vi capsular polysaccharide from Salmonella Typhi to make available a vaccine against typhoid fever that has the potential to also provide broad protection from Streptococcus pneumoniae. High yielding production processes were developed for the purification of PspAs from families 1 and 2. The purified PspAs were conjugated to Vi with high recovery of both Vi and PspA. The processes developed especially for PspA family 2 could readily be adapted for large scale production under cGMP conditions. Previously we have shown that conjugation of diphtheria toxoid (DT) to Vi polysaccharide improves the immune response to Vi but can also enhance the response to DT. In this study it was shown that conjugation of PspA to Vi enhanced the anti-PspA response and that PspA was a suitable carrier protein as demonstrated by the characteristics of a T-cell dependent response to the Vi. We propose that a bivalent vaccine consisting of PspA from families 1 and 2 bound to Vi polysaccharide would protect against typhoid fever and has the potential to also protect against pneumococcal disease and should be considered for use in developing countries.     

Introducing Vi polysaccharide typhoid fever vaccine to primary school children in North Jakarta, Indonesia, via an existent school-based vaccination platform

OBJECTIVES: To report results on coverage, safety and logistics of a large-scale, school-based Vi polysaccharide immunization campaign in North Jakarta. METHODS: Of 443 primary schools in North Jakarta, Indonesia, 18 public schools were randomly selected for this study. Exclusion criteria were fever 37.5 degrees C or higher at the time of vaccination or a known history of hypersensitivity to any vaccine. Adverse events were monitored and recorded for 1 month after immunization. Because this was a pilot programme, resource use was tracked in detail. RESULTS: During the February 2004 vaccination campaign, 4828 students were immunized (91% of the target population); another 394 students (7%) were vaccinated during mop-up programmes. Informed consent was obtained for 98% of the target population. In all, 34 adverse events were reported, corresponding to seven events per 1000 doses injected; none was serious. The manufacturer recommended cold chain was maintained throughout the programme. CONCLUSIONS: This demonstration project in two sub-districts of North Jakarta shows that a large-scale, school-based typhoid fever Vi polysaccharide vaccination campaign is logistically feasible, safe and minimally disruptive to regular school activities, when used in the context of an existing successful immunization platform. The project had high parental acceptance. Nonetheless, policy-relevant questions still need to be answered before implementing a widespread Vi polysaccharide vaccine programme in Indonesia.     

Development of a synthetic Vi polysaccharide vaccine for typhoid fever

Typhoid fever remains a serious public health problem with a high impact on toddlers and young children. Vaccines against the Vi capsular polysaccharide are efficacious against typhoid fever demonstrating that antibodies against Vi confer protection. The currently licensed Vi typhoid vaccines have however limited efficacy and are manufactured by a complex process from wild-type bacteria. Due to these inherent issues with the current vaccines, an alternative vaccine based on an O-acetylated high molecular weight (HMW) polygalacturonic acid (GelSite-OAc™) was generated. The HMW polygalacturonic acid shares the same backbone as the Vi polysaccharide of Salmonella Typhi. The GelSite-OAc™ has a high molecular weight (>1 × 10⁶ Da) and a high degree of O-acetylation (DOAc) (>5 μmole/mg), both exceeding the potency specifications of the current Vi vaccine. Studies in Balb/c mice demonstrated that GelSite-OAc™ was highly immunogenic, inducing a strong antigen-specific antibody response in a DOAc- and dose-dependent manner which was comparable to or higher than those induced by the licensed Vi vaccine. Importantly, the GelSite-OAc™ was shown to be fully protective in mice against lethal challenge with Salmonella Typhi. Furthermore, the GelSite-OAc™ demonstrated a boosting effect or memory response, exhibiting a >2-fold increase in antibody levels upon the second immunization with either GelSite-OAc™ or the Vi vaccine. This novel boosting effect is unique among polysaccharide antigens and potentially makes GelSite-OAc™ effective in people under 2 years old. Together these results suggest that the GelSite-OAc™ could be a highly effective vaccine against Salmonella Typhi.     

伤寒沙门菌Vi抗原作为毒力因子的特性研究

目的　探讨伤寒沙门菌Vi抗原作为毒力因子在致病机理中的作用。方法　选用Vi阳性和Vi阴性伤寒沙门菌作为实验菌株 ,体外考查了Vi抗原在抵抗渗透压 (NaCl)和过氧化物 (H2 O2 )中的作用 ,以及抵抗单核吞噬细胞内化和胞内杀伤的作用。结果　高浓度NaCl明显减少Vi阴性伤寒沙门菌的存活 ;低浓度的H2 O2 对Vi阴性伤寒沙门菌的存活有显著的影响 ;单核吞噬细胞内化和胞内杀伤伤寒沙门菌明显高于对照组。结论　伤寒沙门菌的Vi抗原作为一种毒力因子对其存活于体内及逃避机体的防御机理具有重要作用。