肺炎球菌疫苗的研究进展

肺炎链球菌(即肺炎球菌)导致的疾病在世界各地都是严重的公共健康问题,包括肺炎、脑膜炎、发热性菌血症、中耳炎、鼻窦炎、气管炎等感染.体内外研究显示,肺炎球菌多糖疫苗对成年人肺炎球菌引发的疾病能起到积极的预防作用,但由于多糖疫苗无法刺激产生持续的抗体应答,所以不适用于2岁以下的婴幼儿;而将荚膜多糖与载体蛋白耦联的结合型肺炎球菌疫苗对2岁以下的婴幼儿或免疫缺陷的人群起到积极的保护作用,扩大了使用范围,提高了保护力.本文阐述了预防肺炎球菌疾病疫苗的研究进展,从全菌体疫苗、以菌体荚膜多糖为成分的多糖疫苗直到多糖结合疫苗的发展过程.同时总结了目前国内外结合疫苗的研究现状,认为应将开发安全、有效、价格合理、对肺炎球菌性疾病保护范围广的肺炎球菌疫苗作为高度优先的研究项目.     

肺炎球菌多糖疫苗预防老年肺炎疗效评价

肺炎链球菌为老年肺炎的主要致病菌之一。而关于使用肺炎球菌多糖疫苗可否改变老年人社区获得性肺炎整体危险目前远未清楚。本文意就接种肺炎球菌多糖疫苗在预防老年肺炎中的作用进行了大样本调查。     

肺炎球菌多醣疫苗(由免疫法实行顾问委员会推荐)

美国自1977年起用多价多醣疫苗预防肺炎链球菌引起的疾病。疫苗可预防肺炎球菌性疾病根据有限资料的估计,肺炎球菌肺炎占所有肺炎病例的25%以下。但即使在抗生素时代,它仍然是重要的问题,因为每年尚发生大量病例和死亡。肺炎球菌肺炎可发生在所有年龄组,超过40岁发病率增高。肺炎球菌脑膜炎主要见于年幼儿童,特别是2岁以下。肺炎球菌疾病的死亡率在有菌血症或脑膜炎患者、有潜在内科情况的患者和老年人中最高。慢性病患者,发生肺炎球菌感染的机会明显增加,并且病情更严重,这些病包括镰状细胞性贫血、多发性骨髓瘤、肝硬化、肾功能衰竭、脾功能失调和已行脾切除术者或器官移植者。其他较多发生肺炎球菌感染或病情较严重     

肺炎球菌疫苗预防老年肺炎效用评价

本文作者特就肺炎球菌疫苗对老年肺炎的预防作用进行了评价。研究对象为2837例老人,年龄≥160岁,其中70岁以上者47％,男性37％,女性63％,低危肺炎人群65％,高危肺炎人群35％。研究中,1364例随机接种肺炎球菌并流感杆菌疫苗,纳为PI或治疗组;余     

肺炎球菌疫苗对慢性阻塞性肺疾病的作用及其接种策略进展

肺炎链球菌是导致慢性阻塞性肺疾病（简称慢阻肺）急性加重和合并社区获得性肺炎的重要致病原。肺炎球菌疫苗的接种可以降低慢阻肺患者肺炎的发生率,减少急性加重次数,具有显著的保护作用,但接种时机与复种、疫苗种类选择等尚存争议。本文主要对慢阻肺患者接种肺炎球菌疫苗的相关研究和接种策略进展进行综述。     

非疫苗血清型肺炎链球菌发生机制及疫苗新策略

肺炎链球菌(Streptococcus pneumoniae,Sp)是社区获得性肺炎以及侵袭性疾病如脑膜炎和败血症的主要致病菌之一,到目前为止,关于肺炎链球菌感染性疾病的预防仍以肺炎链球菌多糖疫苗(pneumococcal polysaccharide vaccine,PPV)和肺炎链球菌多糖蛋白结合疫苗(pneumococcal conjugate vaccine,PCV)为主。然而靶向特定荚膜多糖的肺炎链球菌疫苗的选择性压力在一定程度上诱导了肺炎链球菌荚膜转换,导致了不同荚膜抗原突变体的产生,进而造成非疫苗血清型(non-vaccine type,NVT)及无荚膜肺炎链球菌(nonencapsulated streptococcus pneumoniae,NESp)的增加,使现有的疫苗不能有效预防肺炎链球菌的感染。本文重点介绍了肺炎链球菌非疫苗血清型的发生机制,为制备新型肺炎链球菌疫苗提供思路与策略。     

13价肺炎球菌多糖结合疫苗的接种意愿及其影响因素调查分析

目的 针对广州市某2个社区儿童家长进行调查,收集其对13价肺炎球菌多糖结合疫苗的了解、接种意愿等行为状况,为13价肺炎球菌多糖结合疫苗的接种工作提供参考.方法 2017年7月1日-2017年12月31日,针对广州市某2个社区儿童预防接种信息,分别随机抽取各150名在册儿童个案,联系其家长进行面对面的问卷调查.共发放320份问卷,回收有效问卷316份.结果 此次调查中,针对不同文化程度人群进行了13价肺炎球菌多糖结合疫苗的知晓率调查中,大专及以上、高中或中专、初中及以下知晓率为85.33%、50.00%和 53.85%,差异有统计学意义(P<0.01).此外,此次调查中还针对不同家庭收入、不同职业家长进行了调查,其结果 两项调查结果 差异均具有统计学意义(P<0.05).结论 开展预防接种服务工作时,需要发挥各种媒体的优势开展相关知识宣教,从而可以有效提高家长对肺炎球菌性疾病的了解,并对13价肺炎球菌多糖结合疫苗相关知识进行掌握.同时,通过不断健全社区疫苗以及接种管理工作机制,可以更好地为民众提供高效、规范的预防接种服务.     

微卡联合23价肺炎多糖疫苗预防小儿下呼吸道感染的疗效分析

目的研究分析微卡联合23价肺炎多糖疫苗对儿童下呼吸道感染的预防效果及接种后的不良反应,证实微卡联合23价肺炎多糖疫苗的临床疗效。方法随机抽取2-5岁的儿童220人,平均分为疫苗组和对照组两组,各110人;并对疫苗组所有儿童进行随访2周,监测不良反应,同时,对研究对象220人追踪1年,并从下呼吸道感染、抗生素的使用率、住院治疗情况、医疗费用、免疫球蛋白、血红蛋白等方面进行对比。结果接种微卡联合23价肺炎多糖疫苗后,儿童下呼吸道感染的次数和程度明显减少,抗生素的使用率明显降低、住院次数、天数也明显减少,减轻了家长的经济负担;同时,疫苗组的免疫球蛋白及血红蛋白都明显高于对照组,有显著差异(P0.05)。不良反应少,偶尔有局部不良反应,热敷处理或休息12-36 h后均缓解乃至消失。结论接种微卡联合23价肺炎多糖疫苗对2-5岁儿童具有很好的预防和保护效果,并具有较好的经济效益和较高的安全性。     

异基因造血干细胞移植供者接受肺炎球菌结合疫苗后有助于受者产生早期保护抗体反应

接受造血干细胞移植(HSCT)的患者由于免疫缺陷而面临各种感染的危险,并且在相当长时间内,患者对肺炎球菌多糖疫苗(PPV)产生主动免疫的能力受损。本文旨在研究7价肺炎球菌结合疫苗(PCV7)免疫供者后再行移植,能否增强受者移植后早期对免疫疫苗的免疫反应,从而达到预防感染的目的。     

七价肺炎球菌联合疫苗的免疫源性

将含有7个肺炎球菌血清型的多糖抗原的联合肺炎球菌的疫苗分别于2月龄、4月龄和6月龄接种26个健康幼儿,这7种多糖抗原分别为6B,14,19F,23F,18C,4和9V。每种特异抗肺炎球菌多糖被单个结合在B组肺炎球菌的外膜蛋白复合体上。     

Use of pneumococcal polysaccharide vaccines: no simple answers

Control of pneumococcal disease by vaccination with capsular polysaccharide has been investigated and promoted with variable enthusiasm for the past 90 years. Despite this the true value of the 23-valent pneumococcal polysaccharide vaccine remains unclear. In particular the ability of this vaccine to provide durable protection in those who require it most is in greatest doubt. With the introduction of the protein-conjugated pneumococcal polysaccharide vaccines new opportunities for prevention exist, but it will be import to rigorously assess their role in at-risk groups to avoid the uncertainty that surrounds the older simple polysaccharide products.     

Pneumococcal vaccination in adults: does it really work?

The universal burden of pneumococcal disease is high. As pneumococcal capsular antigens induce serotype specific antibodies, both the available vaccines (polysaccharide and polysaccharide conjugated) are able to produce serological response. However, there is reasonable skepticism about the effectiveness and efficacy of the 23-valent polysaccharide vaccine, especially in the elderly and in immunocompromised adults. Results from numerous studies are conflicting but the more recent data suggest that polysaccharide vaccine raises inadequate protection against non-bacteremic pneumonia, while the benefit against invasive pneumococcal disease in high-risk population is uncertain. On the contrary, conjugate vaccine, -originally indicated only for infants and young children- appears to be highly effective but it does not cover the tremendous diversity of pneumococcal serotypes being able to cause disease in adults. Despite this, there is growing evidence that conjugate vaccines, due to their superior immunogenicity, could also be offered for adult vaccination, but still there are certain issues that warrant further investigation.     

Pneumokokkenimpfung

Vaccination is the best protection against severe pneumococcal diseases including infections with resistant pneumococci. Immunocompromised patients, patients with comorbidities, such as chronic renal insufficiency, diabetes mellitus, respiratory and hepatic diseases, infants and elderly patients are at particular risk of invasive pneumococcal diseases. Two different types of vaccines are available: the polysaccharide vaccine with a broad spectrum against 23 serotypes but immunological disadvantages and the conjugate vaccine against 13 serotypes that additionally induces a T-cell dependent immune response generating B-memory cells. Meta-analyses show that polysaccharide vaccine reduces the risk of pneumococcal bacteremia but fails to protect against non-bacteremic pneumonia and is less effective in elderly and immunocompromised patients. Recent data from a randomized controlled trial only presented at international conferences so far, including 85,000 adults over 65 years of age (Community-Acquired Pneumonia Immunization Trial in Adults, CAPiTA) prove that the conjugate vaccine also protects against non-bacteremic pneumonia. Current recommendations still diverge on which type of vaccine should be used in adult patients.     

Pneumococcal antibody levels one decade after immunization of healthy adults

The authors investigated the persistence of anticapsular pneumococcal antibodies in 21 subjects one decade after administration of a single dose of a polyvalent pneumococcal polysaccharide vaccine. Fourteen vaccinees received a hexavalent vaccine composed of the polysaccharides of capsular types 1, 3, 4, 7F, 8, and 12F; four vaccinees received an octavalent vaccine consisting of these six polysaccharides and also those of capsular types 14 and 19F; and three vaccinees received a nonavalent vaccine that also included type 5 capsular polysaccharide. Antibody was measured by radioimmunoassay. The authors detected persistently elevated anticapsular antibody levels among more than one half of vaccinees who developed a significant rise in antibody 1 month following immunization one decade after administration of pneumococcal polysaccharide vaccine when these levels were compared to prevaccine levels for pneumococcal capsular types 4, 7F, and 8. This finding was not the case with pneumococcal types 1, 3, 12F, 14, and 19F; less than two fifths of vaccinees maintained increased levels of anticapsular antibody to these types one decade after administration of pneumococcal vaccine. Geometric mean anticapsular antibody levels for types 7F and 8 only were significantly higher one decade after vaccine administration compared with the levels before immunization (t-test, p less than 0.01).     

Role of cell wall polysaccharide in the assessment of IgG antibodies to the capsular polysaccharides of Streptococcus pneumoniae in childhood.

The interference of antibodies to pneumococcal cell wall polysaccharide (CWPS) in the measurement of antibodies to capsular polysaccharides in children was assessed after vaccination with pneumococcal polysaccharide vaccine. ELISAs were developed to measure IgG subclasses specific for pneumococcal types 3, 6, 19, and 23 and CWPS. Analysis of antibody levels to all four capsular polysaccharides was affected by the presence of antibodies to CWPS, and their removal altered both anti-capsular polysaccharide antibody levels and the interpretation of responses to the vaccine. Thus, it is likely that CWPS contaminating pure capsular polysaccharide reagents used in most standard immunoassays is responsible for falsely elevated measurements of antibodies to capsular polysaccharide and the incorrect assessment of anti-pneumococcal antibody status in childhood.     

Vaccinate your child and save its grandparents from a heart attack? Current perspectives in antipneumococcal vaccination

Streptococcus pneumoniae is an important cause of morbidity and mortality worldwide. There are three established approaches to anti‐pneumococcal vaccination: capsular polysaccharide pneumococcal vaccine (PPV), protein–polysaccharide conjugate pneumococcal vaccine (CPV) and protein‐based pneumococcal vaccine (PBPV). At present, only a 23‐valent PPV for use in adults and a seven‐valent CPV for use in infants are available in clinical practice. This study reviews available data on the efficacy of the available vaccines in different age groups and disease presentations, and the advantages and shortcomings of each type of vaccine, including future perspectives. Special attention is given to controversies regarding the efficacy of PPV against pneumonia in adults and its protective effects against myocardial infarction.     

Prevention of Pneumococcal Meningitis

With the success of the conjugated Haemophilus influenzae type b vaccines, Streptococcus pneumoniae has become one of the most important causes of bacterial meningitis worldwide, causing significant morbidity and mortality. Additionally, the increasing amount of resistance that this organism is developing to multiple classes of antimicrobial agents has made the treatment of pneumococcal infections, especially meningitis, much more difficult. Immunization has been shown to be one of most effective methods for preventing pneumococcal meningitis, resulting not only in a decrease in disease burden, but also a decrease in antimicrobial resistance. Currently, a 23-valent pneumococcal polysaccharide vaccine and a heptavalent protein conjugate vaccine are licensed for use. However, the 23-valent polysaccharide vaccine is poorly immunogenic in infants and young children. The continued development, licensing, and use of pneumococcal conjugate vaccines have the best potential to both prevent disease and decrease the prevalence of pneumococcal meningitis.     

Pneumococcal polysaccharide vaccine in young adults and older bronchitics: determination of IgG responses by ELISA and the effect of adsorption of serum with non-type-specific cell wall polysaccharide

Available pneumococcal vaccines provide only limited protection for certain at-risk populations. Fifteen healthy young adults and 11 older chronic bronchitics received 23-valent pneumococcal vaccine. ELISA showed that IgG reactive with capsular polysaccharides from Streptococcus pneumoniae serotypes 3, 4, 8, 14, and 19F increased after vaccination. Bronchitics exhibited lesser responses for four of these serotypes, although differences between the groups were significant only for serotype 3. Adsorption of postvaccination sera with pneumococcal cell wall polysaccharide significantly reduced mean antibody levels in both groups and lowered the proportion of sera that demonstrated type-specific antibody responses. Reactive IgG was largely restricted to the IgG2 subclass. Pneumococcal vaccine may provide suboptimal protection of older adults because antibody responses to some capsular polysaccharides are lower in elderly bronchitics than in healthy young adults. A substantial proportion of measured antibody reflects IgG reactive with cell wall polysaccharides rather than with type-specific, capsular constituents, suggesting that antibody responses in subjects of all ages deserve reappraisal.     

Specific immunoglobulin-class antibody responses in the elderly before and after 14-valent pneumococcal vaccine

Using an enzyme-linked immunosorbent assay for measuring IgG-, IgA-, and IgM-class antibodies to pneumococcal capsular polysaccharides, we studied responses of debilitated patients 71 to 95 years of age (average, 85 years) in nursing homes to 14-valent pneumococcal vaccine. A control group consisting of normal adults 23 to 41 years of age (average, 27 years) was used for comparison. Normal adults at 28 days postvaccination showed rises in IgG-, IgA-, and IgM-class antibodies to nearly all capsular polysaccharides. The IgG- and IgA-class antibody responses of the elderly patients did not differ significantly from those of the normal adults in most instances. IgM-class responses of the elderly subjects were poor and were significantly lower than those of the control group for six of 14 serotypes. Overall, these studies demonstrate that elderly patients, like healthy younger adults, mount a polyclonal antibody response to pneumococcal polysaccharide vaccine.