Meningococcal factor H binding proteins in epidemic strains from Africa: implications for vaccine development.
Meningococcal factor H binding proteins in epidemic strains from Africa: implications for vaccine development.
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脑膜炎球菌因子H结合蛋白在非洲流行病中的结合蛋白：对疫苗发育的影响。
DOI：
10.1371/journal.pntd.0001302
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发表时间：
2011-09
影响因子：
3.8
通讯作者：
Granoff DM
中科院分区：
文献类型：
--
作者：
Pajon R;Fergus AM;Koeberling O;Caugant DA;Granoff DM
H因子结合蛋白(FHBP)是B群脑膜炎双球菌疫苗的重要抗原。该蛋白与人类因子H(Fh)结合，使细菌能够抵抗血清杀菌活性。关于fHBP在非洲控制脑膜炎球菌流行的疫苗潜力知之甚少，这种流行病通常由非B组菌株引起。我们对来自17个非洲国家的106株A、W-135和X病例分离株的fHBP基因进行了研究。我们检测了重组fHBP疫苗免疫小鼠的抗血清以及高表达fHBP的B组突变株天然外膜泡(NOMV)疫苗的抗血清对补体介导的杀菌活性。其中86株(81%)具有4种常见的fHBP序列变异之一，即变异群1中的ID4/5(A群分离株)、9株(W-135)或74株(X)或变异群2中的ID 22/23(W-135)。超过1/3的A群分离株和2/3的W-135分离株具有低水平的fHBP表达，而所有X分离株均呈中等或高度表达。重组fHBP疫苗的抗血清一般只对fHBP序列变异与相应疫苗ID匹配的分离株具有杀菌作用。低fHBP表达也导致了对抗fHBP杀菌活性的抵抗。与重组疫苗相比，NOMV fHBP ID1疫苗具有广泛的抗fHBP杀菌活性，且抗体抑制fH与fHBP结合的能力强于对照重组fHBP ID1疫苗产生的抗体。来自fHBP表达增加的突变体的NOMV疫苗产生的抗体谱比重组fHBP疫苗具有更强的杀菌活性。NOMV疫苗有望在非洲预防脑膜炎球菌病，并可用于补充最近在一些撒哈拉以南国家引入的A群多糖-蛋白质结合疫苗所提供的覆盖范围。脑膜炎双球菌脑膜炎流行在撒哈拉以南非洲很常见。大多数是由A群囊化血清型菌株引起的，这种菌株在工业化国家很少引起疾病。一种A群多糖蛋白结合疫苗最近在撒哈拉以南非洲的一些国家推出。然而，诱导产生的抗体可能会使A群血清毒株被W-135或X血清群毒株取代，这也会导致该地区的流行。蛋白抗原，如因子H结合蛋白(FHBP)，在预防脑膜炎双球菌B群疾病方面很有前景。这些蛋白也存在于具有其他包膜血清群的菌株中。在这里，我们报告了fHBP疫苗在预防由来自非洲的A、W-135和X群菌株引起的疾病方面的潜力。在所研究的106株非洲分离株中，有4个fHBP氨基酸序列变异株占81%。重组fHBP疫苗在小鼠体内诱导的抗体几乎没有交叉保护活性，但从高表达的fHBP突变株获得的天然外膜囊泡(NOMV)疫苗原型能诱导出具有广泛保护活性的抗体。NOMV疫苗有可能补充A组结合疫苗的覆盖范围，并有助于防止由非A组菌株引起的疾病的出现。
Factor H binding protein (fHbp) is an important antigen for vaccines against meningococcal serogroup B disease. The protein binds human factor H (fH), which enables the bacteria to resist serum bactericidal activity. Little is known about the vaccine-potential of fHbp for control of meningococcal epidemics in Africa, which typically are caused by non-group B strains. We investigated genes encoding fHbp in 106 serogroup A, W-135 and X case isolates from 17 African countries. We determined complement-mediated bactericidal activity of antisera from mice immunized with recombinant fHbp vaccines, or a prototype native outer membrane vesicle (NOMV) vaccine from a serogroup B mutant strain with over-expressed fHbp. Eighty-six of the isolates (81%) had one of four prevalent fHbp sequence variants, ID 4/5 (serogroup A isolates), 9 (W-135), or 74 (X) in variant group 1, or ID 22/23 (W-135) in variant group 2. More than one-third of serogroup A isolates and two-thirds of W-135 isolates tested had low fHbp expression while all X isolates tested had intermediate or high expression. Antisera to the recombinant fHbp vaccines were generally bactericidal only against isolates with fHbp sequence variants that closely matched the respective vaccine ID. Low fHbp expression also contributed to resistance to anti-fHbp bactericidal activity. In contrast to the recombinant vaccines, the NOMV fHbp ID 1 vaccine elicited broad anti-fHbp bactericidal activity, and the antibodies had greater ability to inhibit binding of fH to fHbp than antibodies elicited by the control recombinant fHbp ID 1 vaccine. NOMV vaccines from mutants with increased fHbp expression elicit an antibody repertoire with greater bactericidal activity than recombinant fHbp vaccines. NOMV vaccines are promising for prevention of meningococcal disease in Africa and could be used to supplement coverage conferred by a serogroup A polysaccharide-protein conjugate vaccine recently introduced in some sub-Saharan countries. Epidemics of meningococcal meningitis are common in sub-Saharan Africa. Most are caused by encapsulated serogroup A strains, which rarely cause disease in industrialized countries. A serogroup A polysaccharide protein conjugate vaccine recently was introduced in some countries in sub-Saharan Africa. The antibodies induced, however, may allow replacement of serogroup A strains with serogroup W-135 or X strains, which also cause epidemics in this region. Protein antigens, such as factor H binding protein (fHbp), are promising for prevention of meningococcal serogroup B disease. These proteins also are present in strains with other capsular serogroups. Here we report investigation of the potential of fHbp vaccines for prevention of disease caused by serogroup A, W-135 and X strains from Africa. Four fHbp amino acid sequence variants accounted for 81% of the 106 African isolates studied. While there was little cross-protective activity by antibodies elicited in mice by recombinant fHbp vaccines from each of the four sequence variants, a prototype native outer membrane vesicle (NOMV) vaccine from a mutant with over-expressed fHbp elicited antibodies with broad protective activity. A NOMV vaccine has the potential to supplement coverage by the group A conjugate vaccine and help prevent emergence of disease caused by non-serogroup A strains.
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影响因子：
--
作者：
Chiavolini, Damiana;Weir, Susan;Wetzler, Lee M.
通讯作者：
Wetzler, Lee M.
DOI：
10.1073/pnas.0603940103
发表时间：
2006-07-18
影响因子：
11.1
作者：
Giuliani, Marzia M.;Adu-Bobie, Jeannette;Pizza, Mariagrazia
通讯作者：
Pizza, Mariagrazia
影响因子：
6.4
作者：
Hou, VC;Koeberling, O;Granoff, DM
通讯作者：
Granoff, DM
影响因子：
3.3
作者：
Forgor, AA;Leimkugel, J;Pluschke, G
通讯作者：
Pluschke, G
影响因子：
6.4
作者：
Beernink, P. T.;Caugant, D. A.;Granoff, D. M.
通讯作者：
Granoff, D. M.