Beernink P T, Caugant D A, Welsch J A, Koeberling O, Granoff D M
Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, CA, USA.
J Infect Dis. 2009 May 1;199(9):1360-8. doi: 10.1086/597806.
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.
We investigated fHbp in 35 group A, W-135, and X strains from Africa.
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.
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.
非洲的脑膜炎球菌流行通常由A群菌株引起,但W-135或X群菌株也会在该地区引发流行。结合因子H蛋白(fHbp)是一种正在研究用于B群疫苗的新型抗原。对于来自其他血清群菌株中的fHbp了解甚少。
我们对来自非洲的35株A群、W-135群和X群菌株中的fHbp进行了研究。
22株A群分离株,包括自1963年以来导致流行的每种序列类型(STs),以及来自近期流行的4株X群和3株W-135群分离株,其编码fHbp的基因位于抗原变异组1中。其余6株W-135群分离株具有fHbp变异体2。在每个fHbp变异组内,氨基酸同一性为92%-100%,且所表达的蛋白质具有杀菌单克隆抗体识别的保守表位。从小鼠获得的血清样本,这些小鼠接种了经工程改造表达fHbp变异体的突变体的天然外膜囊泡疫苗,对A群、W-135群或X群菌株具有广泛的杀菌活性。
尽管非洲人群有广泛的自然暴露,但fHbp在非洲菌株中是保守的。表达fHbp变异体的天然外膜囊泡疫苗可能会引发针对该地区所有导致流行的血清群菌株的保护性抗体。