Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870.

Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870.
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DOI:
10.1084/jem.20021911
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发表时间:
2003-03-17
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Pizza M
Pizza M
中科院分区:
其他
文献类型:
--
作者:
Masignani V;Comanducci M;Giuliani MM;Bambini S;Adu-Bobie J;Arico B;Brunelli B;Pieri A;Santini L;Savino S;Serruto D;Litt D;Kroll S;Welsch JA;Granoff DM;Rappuoli R;Pizza M

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由血清群B脑膜炎球菌引起的败血症和脑膜炎是婴儿和年轻人的毁灭性疾病,尚不能通过接种疫苗预防。通过基因组挖掘,我们发现了GNA 1870,这是一种新的脑膜炎奈瑟菌表面暴露的脂蛋白,可诱导高水平的杀菌抗体。该抗原在所有N.脑膜炎测试对71个代表该菌遗传多样性和地理多样性的菌株进行了基因测序。脑膜炎病毒种群,表明该蛋白可以分为三种变体。每个变体内的保守性在91.6%至100%之间,而变体之间的保守性可以低至62.8%。不同菌株的表达水平不同,可分为高、中和低表达子。针对重组形式的蛋白质的抗体引发补体介导的对携带相同变体的菌株的杀伤,并在幼年大鼠模型中诱导被动保护。对那些表达高产蛋白的菌株的杀菌效价最高;然而,即使是非常低的表达者也被有效地杀死。该新抗原是开发针对脑膜炎球菌的新疫苗的最佳候选物。
Sepsis and meningitis caused by serogroup B meningococcus are devastating diseases of infants and young adults, which cannot yet be prevented by vaccination. By genome mining, we discovered GNA1870, a new surface-exposed lipoprotein of Neisseria meningitidis that induces high levels of bactericidal antibodies. The antigen is expressed by all strains of N. meningitidis tested. Sequencing of the gene in 71 strains representative of the genetic and geographic diversity of the N. meningitidis population, showed that the protein can be divided into three variants. Conservation within each variant ranges between 91.6 to 100%, while between the variants the conservation can be as low as 62.8%. The level of expression varies between strains, which can be classified as high, intermediate, and low expressors. Antibodies against a recombinant form of the protein elicit complement-mediated killing of the strains that carry the same variant and induce passive protection in the infant rat model. Bactericidal titers are highest against those strains expressing high yields of the protein; however, even the very low expressors are efficiently killed. The novel antigen is a top candidate for the development of a new vaccine against meningococcus.
纳达(Nada),奈瑟氏菌脑膜炎的新型疫苗候选者。
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发表时间: 2002-06-03
影响因子: 15.3
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发表时间: 1969-06-01
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