WHO关于肺炎链球菌疫苗的意见书

此文介绍了肺炎链球菌感染的流行病学、病原体、肺炎链球菌病、肺炎链球菌疫苗,尤其是23价肺炎链球菌多糖疫苗和结合疫苗以及WHO对该疫苗的意见。     

23价肺炎链球菌多糖疫苗和13价肺炎链球菌结合疫苗在成年人中的应用

 肺炎链球菌是引起全球不同年龄人群,尤其是幼儿和老年人肺炎、败血症和脑膜炎等严重疾病的重要病原菌,由肺炎链球菌导致的这些疾病可以通过疫苗进行预防。在将肺炎链球菌疫苗纳入国家免疫计划的国家,儿童肺炎链球菌病的发病率以及疫苗型肺炎链球菌的携带率大大降低,且可在未免疫人群中产生间接保护作用。此文对23价肺炎链球菌多糖疫苗和13价肺炎链球菌结合疫苗在成年人中的应用进行探讨。     

肺炎链球菌疫苗研究进展

肺炎链球菌疫苗接种是抵抗肺炎链球菌病的最主要策略之一.此文阐述了后7价肺炎链球菌结合疫苗接种时代的肺炎链球菌病的临床和流行特征、新批准的2种肺炎链球菌结合疫苗的应用以及基于蛋白的肺炎链球菌疫苗的研发现状.     

WHO关于23价肺炎链球菌多糖疫苗的意见书

此文简要介绍了肺炎链球菌病及其病原体,评论了23价肺炎链球菌多糖疫苗的安全性、免疫应答和效力,报告了WHO对该疫苗的意见.     

WHO关于23价肺炎链球菌多糖疫苗的意见书

此文简要介绍了肺炎链球菌病及其病原体,评论了23价肺炎链球菌多糖疫苗的安全性、免疫应答和效力,报告了WHO对该疫苗的意见.     

23价肺炎链球菌荚膜多糖疫苗的研制

目的 研制23价肺炎链球菌荚膜多糖疫苗.方法 大罐培养1、2、3、4、5、6B、7F、8、9N、9V、10A、11A、12F、14、15B、17F、18C、19A、19F、20、22F、23F、和33F型肺炎链球菌并进行各型荚膜多糖的纯化,制备23价肺炎链球菌荚膜多糖疫苗.结果 经检定各型精制多糖主要质量指标均符合<欧洲药典>(2005年版)要求.结论 已建立起成熟的细菌培养和多糖纯化工艺.     

23价肺炎链球菌荚膜多糖疫苗的研制

目的 研制23价肺炎链球菌荚膜多糖疫苗.方法 大罐培养1、2、3、4、5、6B、7F、8、9N、9V、10A、11A、12F、14、15B、17F、18C、19A、19F、20、22F、23F、和33F型肺炎链球菌并进行各型荚膜多糖的纯化,制备23价肺炎链球菌荚膜多糖疫苗.结果 经检定各型精制多糖主要质量指标均符合<欧洲药典>(2005年版)要求.结论 已建立起成熟的细菌培养和多糖纯化工艺.     

慢性肺部疾病患者接种23价肺炎链球菌多糖疫苗后抗荚膜多糖抗体的特异性

目的 探讨慢性肺部疾病患者接种23价肺炎链球菌多糖疫苗(PPV)后血清中抗肺炎链球菌荚膜多糖(CPS)IgG抗体的特异性.方法 以39例慢性肺部疾病患者为研究对象,分别用第二代和特异性更高的第三代ELISA测定疫苗接种前、后血清中的肺炎链球菌6B、19F和23F三种血清型的特异性IgG抗体浓度.结果 用第三代ELISA测得的患者血清中血清型特异性IgG抗体水平比用第二代ELISA测得的抗体水平显著降低.无论是PPV接种前的自然感染,还是PPV接种后的主动免疫,慢性肺部疾病患者血中产生的抗CPS-IgG中都有大约一半的非特异性抗体.结论 PPV接种并不能提高慢性肺部疾病患者血中的特异性抗CPS-IgG的比例.     

中山地区儿童呼吸道肺炎链球菌的血清型分布及耐药性

目的了解中山地区儿童呼吸道肺炎链球菌的血清型分布特征及耐药性,为确立当地肺炎链球菌疫苗的组成和疾病防治提供重要的科学依据。方法对2015年本院儿科门诊和住院部诊断为下呼吸道感染患儿的痰标本进行肺炎链球菌分离培养,并进行鉴定及药敏试验。采用多重PCR方法确定血清型。结果 819株肺炎链球菌,主要血清型依次为19F 259株(38.2%)、6型106株(15.6%)、19A 99株(14.6%)、23F 91株(13.4%)、15型40株(5.9%)、3型24株(3.5%)。青霉素耐药肺炎链球菌(PRSP)主要集中在19F和19A。结论中山地区儿童呼吸道肺炎链球菌最常见的血清型为19F、6、19A、23F、15B,19F和19A对抗生素耐药性高于其他血清型。13价疫苗履盖率为89.5%。     

美FDA批准具有更宽保护效力的肺炎球菌13价结合疫苗Prevenar13

目前,美国FDA批准了Pfizer公司旗下Wyeth制药公司开发的肺炎球菌13价结合疫苗（pneumococcal 13-valent conjugate vaccine）Prevenar13,用于出生后6wk至5岁婴、幼儿和儿童的主动免疫接种,以预防由13种血清型肺炎链球菌引起的侵袭性肺炎球菌性疾病,包括菌血症、脓毒症、脑膜炎和肺炎及由7种血清型肺炎链球菌引起的中耳炎。     

13-valent pneumococcal conjugate vaccine

The 7-valent pneumococcal conjugate vaccine (4, 6B, 9V, 14, 18C, 19F, 23F) is the standard vaccine for the prevention of invasive pneumococcal infections in infants and children under 5 years of age. A 13-valent pneumococcal conjugate vaccine (with the addition of valences 1, 3, 5, 6A, 7F and 19A) has now been authorised to replace the 7-valent vaccine within the European Union. This new vaccine, adapted to recent epidemiological data on invasive pneumococcal infections, is supposed to cover at least 80% of pneumococcal infections in Europe. The protective potency of the 13-valent vaccine has not yet been tested in clinical trials. Clinical evaluation is based on two immunogenicity studies, in which the immunogenic potency of the 13-valent vaccine was similar to that of the 7-valent vaccine for their shared serotypes, but lower for serotypes 3, 6B and 9V. For these last two serotypes and for the new serotypes, the usual target antibody titre was reached after a booster injection. This was not the case for valence 3. * The vaccine used in immunogenicity studies did not contain polysorbate 80 (an excipient), and a non-inferiority study of the marketed vaccine containing polysorbate 80 was therefore conducted in 500 children. Non-inferiority was established for all 13 valences after the booster injection, but not for valences 6B and 23F after primary vaccination. According to the results of 10 studies, simultaneous administration of the 13-valent pneumococcal conjugate vaccine does not affect the immunogenicity of other vaccines generally administered before the age of 5 years. Other immunogenicity studies support the use of a variety of vaccine schedules for infants and children under 5 years of age who have not yet been vaccinated or who have started vaccination with the 7-valent vaccine. Increasing the number of valences in the vaccine from 7 to 13 led to no marked increase in local adverse effects (hypersensitivity, indurations, erythema) or systemic reactions (mainly fever, decreased sleep and irritability). In practice, replacing the 7-valent pneumococcal conjugate vaccine with the 13 valence vaccine could lead to a further reduction in the incidence of invasive pneumococcal infections. However, this remains to be confirmed by well-conducted epidemiological follow-up studies.     

Advances in pneumococcal vaccines: what are the advantages for the elderly?

Streptococcus pneumoniae causes considerable morbidity and mortality in the elderly. There are three established approaches to pneumococcal vaccination: polysaccharide vaccines, protein-polysaccharide conjugate vaccines and protein-based vaccines. This article reviews advances in anti-pneumococcal vaccines, with reference to advantages and shortcomings for the elderly in particular. The 23-valent polysaccharide pneumococcal vaccine (PPV) is currently recommended for high-risk patients and the general elderly population. Although the effectiveness of PPV against pneumonia is unclear, recent studies point to significant protective effects in preventing pneumococcal pneumonia and reducing the severity of disease in vaccinated elderly patients. PPV offers high serotype coverage and, although it is poorly immunogenic in some individuals, provides approximately 60% protection against invasive disease in the general elderly population. PPV vaccination appears cost effective for elderly patients although the vaccine might only be effective in preventing invasive disease. Additional benefits could mean a greater level of vaccine cost effectiveness. However, it is important to understand that PPV provides incomplete protection, especially in those with underlying high-risk conditions, and development of more effective pneumococcal vaccination strategies for elderly patients is still needed. In recent years, the most important advance in the prevention of pneumococcal infections in the elderly has been the introduction of a 7-valent conjugate pneumococcal vaccine (CPV) as a routine vaccination for infants. In addition to dramatically reducing invasive infection in children, CPV has been observed to have a considerable indirect protective effect in parents and grandparents. While the possibility of using CPV in elderly patients has been suggested, currently there are only limited immunogenicity data and no efficacy data in adults. The low serotype coverage is an important shortcoming and if CPV were to be used in the elderly, it would need to be given sequentially with the PPV. New CPVs covering more serotypes are currently under investigation, and these could be an alternative for use in all groups in the future. Numerous protein-based vaccine candidates offer the potential advantage of prevention against infections caused by all pneumococcal serotypes. Several are in various stages of development in animal models, but none can be expected to be available in clinical practice for several years at least. To date, the 23-valent PPV is still the best anti-pneumococcal vaccine option in the management of elderly persons. Introduction of the 7-valent CPV as a routine vaccine for children has provided considerable indirect benefits for older adults via herd immunity, but this vaccine has limited serotype coverage in elderly individuals. New CPVs including more serotypes (various CPVs are in different phases of pre-licensure studies) could prove to be good options in the future for all age groups. Several protein-based pneumococcal vaccine candidates (currently under investigation in animal models) offer the potential advantage of serotype independent protection, but none can be expected to be available in clinical practice in the near future.     

7-valent pneumococcal conjugate vaccine: new preparation. Prevents rare invasive infections in infants

(1) Infants under two years of age are the children most exposed to invasive pneumococcal infections (meningitis and bacteraemia). The estimated incidence in France is about 45 cases per year per 100,000 in the first year of life. The 23-valent pneumococcal polysaccharide vaccine is ineffective in children under two years of age. (2) Marketing authorization has now been granted for a 7-valent pneumococcal conjugate vaccine for children under two years. It is the first pneumococcal vaccine specifically designed for this age group. (3) Its immunogenicity in 2 year old children has been carefully documented. (4) A comparative, randomised, double-blind trial involving nearly 38,000 Californian infants showed a lower incidence of both all invasive pneumococcal infections (approximately 1 case avoided per 400 children vaccinated), and those due to the 7 serotypes covered by the vaccine. (5) These results are not directly applicable to France, where the pneumococcal serotype distribution (especially the 7 serotypes covered by the vaccine) seems to be somewhat different, and where the incidence of invasive pneumococcal infections is much lower. (6) The 7-valent vaccine has not been assessed adequately in children who are at high risk for invasive pneumococcal infection. Some small studies of children with sickle-cell disease show adequate immunogenicity. (7) The known adverse effects of the 7-valent vaccine are acceptable, mainly comprising local reactions and fever. (8) The risk of an epidemiological shift towards serotypes not covered by the vaccine (through pharyngeal carriage and invasive infection) cannot been ruled out. In otitis media, an increase in pneumococcal infections due to serotypes not covered by the vaccine negates the benefit of vaccination. (9) In practice, considering the severity of invasive pneumococcal infections and the documented efficacy and safety of the 7-valent conjugate vaccine, vaccination is warranted for individual children under two years of age, especially those at risk, but epidemiological monitoring and pharmacovigilance must continue.     

疫苗0～2 ℃储存挑战性实验

目的  探讨冻干制剂乙型脑炎减毒活疫苗和液体制剂23价肺炎球菌多糖疫苗0～2 ℃条件下存放对其效价的影响。方法  将冻干制剂乙型脑炎减毒活疫苗和液体制剂23价肺炎球菌多糖疫苗存放于0～2 ℃条件下一定时间后,与存放于2～8 ℃规定条件的制品进行疫苗效价的比较。结果  1人份和5人份乙型脑炎减毒活疫苗在0～2 ℃条件下分别存放17 h 20 min和18 h 55 min,病毒滴度均符合5.7～7.1 lgPFU/ml的质量标准,且与存放于2～8 ℃规定条件的同批次疫苗比较,t值分别为0.26和0.28,P值均大于0.05,差异无统计学意义;23价肺炎球菌多糖疫苗在0～2 ℃条件下存放21 h 50 min,23个型别的多糖含量均符合35～65 μg/ml的质量标准,且与存放于2～8 ℃规定条件的同批次疫苗比较,t值为0.01~2.25,P值均大于0.05,差异无统计学意义。结论  冻干制剂乙型脑炎减毒活疫苗和液体制剂23价肺炎球菌多糖疫苗存放在0～2 ℃条件下的一定时间内,疫苗效价仍符合质量标准。     

Infant immunisation with a pneumococcal conjugate vaccine: from the age of two months, for all infants

(1) In France, before widespread infant immunisation with the 7-valent pneumococcal conjugate vaccine, there were about 13 deaths a year and about 145 cases of pneumococcal meningitis, often with serious sequelae. The peak incidence of pneumococcal meningitis occurs at approximately 5 months of age. (2) About 65% of the pneumococcal serotypes that cause meningitis in French children are covered by the 7-valent vaccine. (3) Several trials have yielded similar results: vaccination during infancy reduces the risk of invasive pneumococcal infection due to serotypes covered by the vaccine by 80% to 90%, leading to a relative reduction of 60% to 70% in the risk of invasive pneumococcal infections due to all serotypes. (4) In the United States, since the introduction of routine vaccination for all infants under 2 years of age, infant mortality due to invasive pneumococcal infections has fallen, with roughly one death prevented per 200 000 infants. Infant vaccination also appears to reduce the circulation of vaccine serotypes among unvaccinated subjects, especially those over 50 years of age. There is some evidence of replacement by non-vaccine serotypes, but the magnitude of occurrence is small. (5) The efficacy of the 7-valent pneumococcal conjugate vaccine in the prevention of acute otitis media in infants has been tested in several clinical trials: it is minimal to non-existent. (6) The adverse effects of the 7-valent pneumococcal conjugate vaccine are similar to those of other commonly used vaccines, and include fever, rash, urticaria, reactions at the injection site, and agitation. Serious allergic reactions have occurred: at least one spontaneous report of one serious allergic reaction per 500 000 vaccinated children. (7) There is consensus on the vaccination schedule: 3 intramuscular injections given at least 4 weeks apart, plus a booster at 12-15 months, if vaccination is started at 2 months of age. (8) In France, routine vaccination would prevent about a dozen deaths, several dozen cases of meningitis, and a few hundred hospital admissions per year, at a cost of at least one serious allergic reaction. (9) The risk-benefit balance is very favourable in infants who are at a high risk of invasive pneumococcal infection. It is also positive in other infants, and should therefore be routinely offered from the age of 2 months. Epidemiological monitoring must continue.     

Pneumococcal disease in the elderly: what is preventing vaccine efficacy?

The effective prevention of Streptococcus pneumoniae infection has a renewed priority in an era in which the emergence of antibacterial-resistant strains has the potential to further compromise efforts to reduce early mortality from invasive pneumococcal infection. Although the 23-valent pneumococcal polysaccharide (PPS) vaccine was approved in the US to prevent respiratory and invasive infection in the elderly and other high-risk populations, the protective efficacy of this vaccine for the growing population of adults aged >65 years remains controversial. The apparent effectiveness of pneumococcal immunisation in clinical studies of elderly adults has varied depending upon whether a reduction in pneumococcal colonisation, pneumonia, bacteraemia or death was used as an outcome. Clinical studies of vaccine efficacy to date suggest that the current pneumococcal vaccine is 56 to 81% effective at preventing invasive pneumococcal infection, and may have additive benefit to influenza vaccine in preventing community-acquired pneumonia, particularly in elderly adults with an increased risk of serious pneumonia requiring hospitalisation. Possible reasons for incomplete protection from pneumococcal infection after immunisation include infection with non-vaccine serotypes, inadequate or ineffective antibody responses, waning of antibody responses, or compromised nonhumoral host defences. Further studies are needed to determine whether: (i) elderly adults who respond poorly to the 23-valent pneumococcal vaccine can be identified prior to immunisation and targeted for study with improved pneumococcal vaccines; (ii) specific nutrient deficiencies can be identified and corrected to improve the immune responsiveness of elderly adults to the PPS vaccine; (iii) newer protein-conjugate or DNA pneumococcal vaccines may be more uniformly immunogenic for elderly adults; and (iv) whether smoking cessation reduces the risk of invasive pneumococcal infection in elderly adults.     

Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed) [prevenar 13®

The pneumococcal polysaccharide conjugate vaccine Prevenar 13? (PCV13) comprises 13 capsular Streptococcus pneumoniae polysaccharide serotypes that are individually conjugated to nontoxic diphtheria protein (cross-reactive material [CRM(197)]). In randomized, comparator-controlled, phase III trials in healthy infants aged 2-6 months, PCV13 elicited a strong immune response against all 13 pneumococcal serotypes in terms of the proportion of vaccinees achieving reference antibody levels with a two- or three-dose primary vaccination series. Immune responses for the seven serotypes common to PCV13 and the 7-valent pneumococcal conjugate vaccine Prevenar? (PCV7) were generally similar. Antibodies to all vaccine serotypes were functional. A booster dose of PCV13 administered between 11 and 15 months of age generally boosted the immune response against all 13 serotypes, regardless of whether infants had previously received PCV13 or PCV7 during the primary vaccination phase. Robust immune responses against all serotypes were achieved when PCV13 was administered as catch-up vaccination schedules in older infants and young children aged 7-72 months. Importantly, PCV13 did not interfere with the immune responses to coadministered routine paediatric vaccines. Based on data for PCV7, it is expected that PCV13 will also display protective efficacy against invasive pneumococcal disease, otitis media and pneumonia. PCV13 was generally well tolerated, with an adverse event profile similar to that of PCV7 after any vaccine dose.     

23价肺炎球菌多糖疫苗定量检定质量趋势分析

目的:统计分析2006-2011年生产的140批23价肺炎球菌多糖疫苗的5项定量检定指标,为疫苗的质量评价和质量监督提供依据。方法:对2006-2011年生产的140批23价肺炎球菌多糖疫苗的多糖含量、苯酚含量、氯化钠含量、pH值、细菌内毒素检查等5项指标的检定结果进行统计分析;对各单型多糖的含量进行移动标准偏差分析;对苯酚含量、氯化钠含量、pH值测定、细菌内毒素检查指标进行移动平均值总体趋势分析。结果:6年来,23价肺炎球菌多糖疫苗的多糖含量批间差异逐渐缩小;苯酚含量、氯化钠含量、细菌内毒素检查均值逐渐下降并趋于稳定;pH值一直较为稳定。结论:2006-2011年生产的23价肺炎球菌多糖疫苗质量逐步提高并保持稳定。