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用于评估VA-MENGOC-BC对B群脑膜炎奈瑟菌临床分离株有效性的高铁血症小鼠模型。

The hyperferremic mouse model for the evaluation of the effectiveness of VA-MENGOC-BC against Neisseria meningitidis B clinical isolates.

作者信息

Sifontes S, Infante J F, Pérez P, Caro E, Sierra G, Campa C

机构信息

Centro de Bioactivos Químicos, Universidad Central, Las Villas, Habana, Cuba.

出版信息

Arch Med Res. 1997 Spring;28(1):41-5.

PMID:9078586
Abstract

VA-MENGOC-BC is a vaccine against B and C serogroups of Neisseria meningitidis. Its effectiveness at population level has been shown after the application of the vaccine in Cuba, Brazil, Argentina and Colombia. In vitro assays are not always able to reproduce the microorganism-host relationships and this makes it necessary to compile and standardize results obtained in animal models to extrapolate them with a greater degree of safety for humans. We evaluated the effectiveness of VA-MENGOC-BC against Neisseria meningitidis group B isolates from clinically ill patients in Latin America (Argentina, B not typeable: P1; Chile, not typed; Colombia, B4:P1.15 and Cuba B4:P1.15) using Balb/cJ mice treated with iron to make them susceptible to Neisseria meningitidis. The lethal median dose of each strain and of two others that were not included in challenge assays (Brazil: P1.15 and Argentina, B2b:P1.10) were determined. Results were 2.68 x 10(6), 3.16 x 10(7), 1.98 x 10(8), 1.28 x 10(9), 6.42 x 10(6) and 3.88 x 10(7) colony forming units (CFU), respectively. Non-immunized animals and mice treated with one and two doses of VA-MENGOC-BC were challenged with 10(3)-(10) CFU. Protection ranged from 30 to 100% with one dose and was equal to or higher than 70% with the two-dose immunization schedule. A significant protection could not be observed against the Colombian isolate from the lethality point of view, but the mean time of survival lengthened in immunized animals in relation to the controls. The applied inoculum of this strain was much higher (505 x LD50) than the remaining ones. The protection conferred was evident; nevertheless, more data are needed to determine how relevant the results are to humans.

摘要

VA-MENGOC-BC是一种针对脑膜炎奈瑟菌B和C血清群的疫苗。在古巴、巴西、阿根廷和哥伦比亚应用该疫苗后,已显示出其在人群层面的有效性。体外试验并不总能重现微生物与宿主的关系,因此有必要汇总和标准化在动物模型中获得的结果,以便更安全地外推至人类。我们使用经铁处理使其易感染脑膜炎奈瑟菌的Balb/cJ小鼠,评估了VA-MENGOC-BC对拉丁美洲临床患病患者中分离出的B群脑膜炎奈瑟菌(阿根廷,B不可分型:P1;智利,未分型;哥伦比亚,B4:P1.15和古巴B4:P1.15)的有效性。确定了每种菌株以及另外两种未用于攻毒试验的菌株(巴西:P1.15和阿根廷,B2b:P1.10)的半数致死剂量。结果分别为2.68×10⁶、3.16×10⁷、1.98×10⁸、1.28×10⁹、6.42×10⁶和3.88×10⁷菌落形成单位(CFU)。用10³ - 10⁵CFU对未免疫动物以及用一剂和两剂VA-MENGOC-BC处理的小鼠进行攻毒。一剂疫苗的保护率为30%至100%,两剂免疫方案的保护率等于或高于70%。从致死率角度来看,未观察到对哥伦比亚分离株有显著保护作用,但与对照组相比,免疫动物的平均存活时间延长。该菌株的接种量(505×LD50)比其他菌株高得多。所赋予的保护作用是明显的;然而,还需要更多数据来确定这些结果与人类的相关性。

相似文献

1
The hyperferremic mouse model for the evaluation of the effectiveness of VA-MENGOC-BC against Neisseria meningitidis B clinical isolates.用于评估VA-MENGOC-BC对B群脑膜炎奈瑟菌临床分离株有效性的高铁血症小鼠模型。
Arch Med Res. 1997 Spring;28(1):41-5.
2
Evaluation of the antimeningococcal immunoglobin activity against five strains of Neisseria meningitidis group B from Latin America using mice as model.
Arch Med Res. 1997 Winter;28(4):591-5.
3
Outer membrane vesicles (OMVs) and detoxified lipooligosaccharide (dLOS) obtained from Brazilian prevalent N. meningitidis serogroup B strains protect mice against homologous and heterologous meningococcal infection and septic shock.从巴西流行的B群脑膜炎奈瑟菌菌株中获得的外膜囊泡(OMV)和解毒脂寡糖(dLOS)可保护小鼠免受同源和异源脑膜炎球菌感染及败血性休克。
Vaccine. 2004 Jun 30;22(20):2617-25. doi: 10.1016/j.vaccine.2003.12.009.
4
Biodistribution of the Cuban anti-meningococcal vaccine, VA-MENGOC-BC, in Balb/c mice.
Arch Med Res. 1997 Spring;28(1):37-40.
5
[Humoral immune response to the proteins of an antimeningococcal BC vaccine in a trial carried out in Antioquia, Colombia].
Bol Oficina Sanit Panam. 1995 Apr;118(4):285-94.
6
Immunization of mice with Neisseria meningitidis serogroup B genomic expression libraries elicits functional antibodies and reduces the level of bacteremia in an infant rat infection model.用B群脑膜炎奈瑟菌基因组表达文库免疫小鼠可引发功能性抗体,并降低幼鼠感染模型中的菌血症水平。
Vaccine. 2005 Jan 4;23(7):932-9. doi: 10.1016/j.vaccine.2004.07.032.
7
[Meningococcal disease and VA-MENGOC BC in minors less than 1 year of age. Cuba, 1983 to 1991].
Rev Cubana Med Trop. 1996;48(1):34-9.
8
[The post-licensing efficacy of VA-MENGOC-BC in children under 6 in Holguín, Cuba. The first year of observation].[古巴奥尔金省VA-MENGOC-BC对6岁以下儿童的上市后疗效。第一年观察]
Rev Cubana Med Trop. 1995;47(1):59-64.
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[Humoral immune response to the capsular polysaccharide of Neisseria meningitidis serogroup C in an antimeningococcal BC vaccination trial in Antioquia, Colombia].[在哥伦比亚安蒂奥基亚进行的一项抗脑膜炎球菌BC疫苗试验中,对C群脑膜炎奈瑟菌荚膜多糖的体液免疫反应]
Bol Oficina Sanit Panam. 1995 Apr;118(4):295-301.
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[Immunogenecity induced by the VA-MENGOC-BC antimeningococcal vaccine against the ATCC C11. N. meningitidis strain in adolescents 12 years after being vaccinated].
Rev Cubana Med Trop. 2004 Jan-Apr;56(1):26-30.

引用本文的文献

1
Protection by natural human immunoglobulin M antibody to meningococcal serogroup B capsular polysaccharide in the infant rat protection assay is independent of complement-mediated bacterial lysis.在幼鼠保护试验中,天然人免疫球蛋白M抗体对B群脑膜炎球菌荚膜多糖的保护作用不依赖补体介导的细菌裂解。
Infect Immun. 2005 Aug;73(8):4694-703. doi: 10.1128/IAI.73.8.4694-4703.2005.
2
A glycoconjugate vaccine for Neisseria meningitidis induces antibodies in human infants that afford protection against meningococcal bacteremia in a neonate rat challenge model.一种针对脑膜炎奈瑟菌的糖缀合物疫苗可在人类婴儿中诱导产生抗体,这些抗体在新生大鼠攻毒模型中能提供针对脑膜炎球菌血症的保护作用。
Infect Immun. 2002 Dec;70(12):6576-82. doi: 10.1128/IAI.70.12.6576-6582.2002.