Meningococcal Factor H-Binding Protein Variants Expressed by Epidemic Capsular Group A, W-135, and X Strains from Africa
Meningococcal Factor H-Binding Protein Variants Expressed by Epidemic Capsular Group A, W-135, and X Strains from Africa
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DOI：
10.1086/597806
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发表时间：
2009-05-01
影响因子：
6.4
通讯作者：
Granoff, D. M.
中科院分区：
文献类型：
--
作者：
Beernink, P. T.;Caugant, D. A.;Granoff, D. M.
背景。非洲的脑膜炎球菌流行通常由荚膜群A菌株引起，但W-135或X菌株也在该地区引起流行。因子h结合蛋白（fHbp）是一种正在研究用于B组疫苗的新型抗原。对其他荚膜群菌株中fHbp的含量了解甚少。我们对来自非洲的35株A组、W-135组和X组的fHbp进行了检测。22个A组分离株（包括1963年以来导致流行的每种序列类型（STs））和4个X组分离株和3个W-135组分离株（来自最近流行的）在抗原变异组1中含有编码fHbp的基因。其余6株W-135分离株为fHbp变体2。各fHbp变异组氨基酸同源性为92% ~ 100%，表达的保守表位被杀菌单克隆抗体识别。用表达fHbp变异体的天然外膜囊泡疫苗接种小鼠的血清样本，对A组、W-135组和X组菌株具有广泛的杀菌活性。尽管非洲人口有广泛的自然暴露，但fHbp在非洲菌株中是保守的。一种表达fHbp变体的天然外膜囊泡疫苗可能会引发保护性抗体，抵抗所有在该地区引起流行病的荚膜群菌株。
Background. Meningococcal epidemics in Africa are generally caused by capsular group A strains, but W-135 or X strains also cause epidemics in this region. Factor H-binding protein (fHbp) is a novel antigen being investigated for use in group B vaccines. Little is known about fHbp in strains from other capsular groups.Methods. We investigated fHbp in 35 group A, W-135, and X strains from Africa.Results. The 22 group A isolates, which included each of the sequence types (STs) responsible for epidemics since 1963, and 4 group X and 3 group W-135 isolates from recent epidemics had genes encoding fHbp in antigenic variant group 1. The remaining 6 W-135 isolates had fHbp variant 2. Within each fHbp variant group, there was 92%-100% amino acid identity, and the proteins expressed conserved epitopes recognized by bactericidal monoclonal antibodies. Serum samples obtained from mice vaccinated with native outer membrane vesicle vaccines from mutants engineered to express fHbp variants had broad bactericidal activity against group A, W-135, or X strains.Conclusions. Despite extensive natural exposure of the African population, fHbp is conserved among African strains. A native outer membrane vesicle vaccine that expresses fHbp variants can potentially elicit protective antibodies against strains from all capsular groups that cause epidemics in the region.