A randomized,phase 1/2 trial of the safety,tolerability, and immunogenicity of bivalent rLP2086 meningococcal B vaccine in healthy infants

Background

Neisseria meningitidis serogroup B (MnB) is a major cause of invasive meningococcal disease in infants. A conserved, surface-exposed lipoprotein, LP2086 (a factor H-binding protein [fHBP]), is a promising MnB vaccine target. A bivalent, recombinant vaccine targeting the fHBP (rLP2086) of MnB was developed.

Methods

This phase 1/2 clinical study was designed to assess the immunogenicity, safety, and tolerability of a 4-dose series of the rLP2086 vaccine at 20-, 60-, 120-, or 200-μg dose levels in vaccine-naive infants when given with routine childhood vaccines. The study was to consist of two phases: a single-blind sentinel phase and an open-label full enrollment phase. During the sentinel phase, randomization of subjects to the next higher dose was delayed pending a 14-day safety review of dose 1 of the preceding dose cohort. The full enrollment phase was to occur after completion of the sentinel phase.

Results

Local reactions were generally mild and adverse events infrequent; however, after only 46 infants were randomized into the study, fever rates were 64% and 90% in subjects receiving one 20- or 60-μg rLP2086 dose, respectively. Most fevers were <39.0 °C. Only 2 subjects in the 20-μg group and 1 subject in the 60-μg group experienced fevers >39.0 °C; no fevers were >40.0 °C. Due to these high fever rates, the study was terminated early. No immunogenicity data were collected. This report discusses the safety and acceptability of rLP2086 in infants after one 20- or 60-μg dose.

Conclusion

Due to the high fever rate experienced in the 20- and 60-μg groups, rLP2086 in the current formulation may not be acceptable for infants.     

韶关市2009—2011年健康人群C群脑膜炎奈瑟菌血清杀菌力抗体检测结果分析

目的了解韶关市健康人群血清C群脑膜炎奈瑟菌杀菌力水平,以评价健康人群对C群脑膜炎奈瑟菌的保护水平。方法2009—2011年,每年随机抽取8个年龄组健康人群血清共计811份,采用血清杀菌力试验检测血清中杀菌力抗体水平。结果811份健康人群血清中C群脑膜炎奈瑟菌杀菌力抗体总阳性率为25．40％,总保护率为23．06％,GNT为l：5．13,95％置信区间1：4．57～1：5．89。结论韶关市健康人群对c群脑膜炎奈瑟菌的传染有易感性,年龄越低其对C群脑膜炎奈瑟菌的抵抗力越弱,应加大对A＋C群流脑疫苗宣传力度,普及适龄儿童A＋C群流脑疫苗的免疫接种。     

Serogroup C Neisseria meningitidis invasive infection: analysis of the possible vaccination strategies for a mass campaign

The serogroup C meningococcal conjugate vaccine is available since 1999. In the absence of randomized controlled trials that support a specific schedule, each country has adopted different vaccination programmes. Hereby, we analyse positive and negative aspects of the different vaccination strategies. Conclusion: While waiting for the introduction of other antimeningococcal vaccines, covering also for the Group B meningococci, further studies on effectiveness of an optimal schedule to be adopted in European countries are needed.     

Vaccines against meningococcal disease: current and future technologies

Development of the meningococcal serogroup C conjugate vaccine and its national implementation in the UK has been a major breakthrough in the prevention of meningococcal disease. New technologies are increasing the likelihood that research towards a vaccine against group B meningococcus will be successful. This review covers the recent development of vaccines against meningococcal disease and examines future vaccine candidates. The development of meningococcal polysaccharide vaccines was based on the virulence of the bacterial capsule components. The immunogenicity of these vaccines has been improved by covalent linkage to proteins in the new meningococcal C conjugate vaccines. However, the most promising developments for serogroup B disease have stemmed from other virulence determinants such as outer membrane proteins (OMPs) and lipopolysaccharides (LPS). New genome sequencing technology promises a way forward to developing a broadly cross-protective vaccine for this important pathogen.     

97例流行性脑脊髓膜炎患者的临床特征及流行病学分析

目的总结2008年以来四川省渠县流行性脑脊髓膜炎(流脑)的临床特征,为今后流脑防治工作积累经验。方法对97例流脑患者的临床资料进行回顾性分析,统计分析采用卡方检验。结果患者主要集中在青少年和成人,分别为43例(占44.6%)和34例(35.4%),婴幼儿最少,仅6例(6.2%)。临床分型以普通型为主,占72.3%,暴发型占27.7%。死亡7例(7.7%),共分离出49株脑膜炎奈瑟菌,培养阳性率为50.8%(49/97),其中,血培养阳性率为44.6%(43/97),脑脊液培养阳性者占31.4%(30/97)。药物敏感结果显示,无论是C群脑膜炎奈瑟菌还是其他群,对青霉素、头孢曲松、头孢噻肟等普遍敏感,而对复方磺胺甲噁唑、庆大霉素、环丙沙星等耐药率在80%以上。血清学分类显示,高达82.8%(80/97)的患者为C群菌株感染,与其他群流脑比较,C群感染者病重,病死率高。结论C群脑膜炎奈瑟菌已成为目前四川省渠县流脑流行的主要菌株,C群感染者多见于青少年和成人。治疗以青霉素、第三代头孢菌素类抗生素为佳。     

滁州市2004~2005年C群流脑流行特征分析

目的研究滁州市C群流脑的流行特征与控制措施,为今后C群流脑防控工作提供科学依据。方法对2004~2005年度流脑个案调查、实验室检测结果进行分析。结果28例流脑患者中检出5例C群Nm,病例的密切接触者中检出4株C群Nm;在地区分布中,南谯区乌衣镇中学发生5例C群流脑为局部爆发,其余为散发病例;病倒中学生占71.42%,10~20岁年龄组占71.42%;有A群流脑疫苗免疫史占82.14%,有5例流脑A C二价疫苗免疫失败。结论C群流脑病例来势凶猛,病程进展快,病死率高;接种A群流脑疫苗不能阻止C群流脑流行;为防止发病控制疫情扩散,应对20岁以下人群和在校的大、中专学生等易感群体提供免疫保护。     

C群脑膜炎球菌多糖蛋白结合疫苗衍化工艺研究

目的筛选和优化C群脑膜炎多糖的衍化工艺。方法将C群奈瑟脑膜炎球菌多糖经溴化氰活化后通过己二酰肼衍生后制备出适宜的多糖衍生物。对衍化条件进行摸索和优化后通过衍化率及衍生物的可溶性来考察衍化效果,同时通过生化指标来考察该衍生工艺制备的结合疫苗的质量和收率。结果在pH11.0±0.2、活化30min以及溴化氰与多糖比值(W/W)=0.5时,所获衍生物制备的结合疫苗各项生化指标在所筛选的条件中最优。结论经过筛选优化的衍生工艺提高了多糖的衍化率,适于结合疫苗的研制,保证了结合疫苗的免疫原性。     

Space-time cluster analysis of invasive meningococcal disease

Clusters are recognized when meningococcal cases of the same phenotypic strain (markers: serogroup, serotype, and subtype) occur in spatial and temporal proximity. The incidence of such clusters was compared to the incidence that would be expected by chance by using space-time nearest-neighbor analysis of 4,887 confirmed invasive meningococcal cases identified in the 9-year surveillance period 1993-2001 in the Netherlands. Clustering beyond chance only occurred among the closest neighboring cases (comparable to secondary cases) and was small (3.1%, 95% confidence interval 2.1%-4.1%).     

健康人群流行性脑脊髓膜炎流行前期和流行期A、C群脑膜炎奈瑟菌抗体水平研究

目的掌握合肥市健康人群A、C群脑膜炎奈瑟菌(Nm)抗体水平现状。方法应用重复横断面监测研究模式,以合肥市辖3县4区划分为7个研究地区,在2005-2006,2006-2007年流行性脑脊髓膜炎(流脑)流行季节流行前期和流行期,采用整群重复抽样方法,应用酶联免疫吸附试验,对健康人群A、C群Nm抗体水平进行调查。结果连续监测健康人群2次流行前期和流行期,实际抽样范围672～690人。2次流行前期和流行期之间A群无差异,C群差异有统计学意义;2次流行期之间A、C群差异均有统计学意义。0～5岁和≥21岁组相对较低,11～15岁、16～20岁、≥21岁组流行期明显上升。同期不同地区之间差异均有统计学意义,肥西县、长丰县呈现明显低抗体水平。结论健康人群中存在一定A、C群Nm抗体水平,结合现状应确保儿童和青少年疫苗有效接种率,加强成人流脑预防控制工作。