Influence of sequence variability on bactericidal activity sera induced by Factor H binding protein variant 1.1
Influence of sequence variability on bactericidal activity sera induced by Factor H binding protein variant 1.1
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DOI：
10.1016/j.vaccine.2010.11.064
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发表时间：
2011-01-29
期刊：
影响因子：
5.5
通讯作者：
Serruto, Davide
中科院分区：
文献类型：
--
作者：
Brunelli, Brunella;Del Tordello, Elena;Serruto, Davide
H因子结合蛋白（fHbp）是针对血清群B脑膜炎球菌的新型疫苗的主要抗原之一，在不同的临床分离株中其氨基酸序列和表达水平有所不同。为了评估氨基酸序列变异性对疫苗覆盖率的贡献，我们构建了仅对抗fHbp抗体的杀菌杀伤敏感的菌株，并将其工程化以从组成型启动子表达相等水平的10种不同fHbp亚变体。对这些等基因菌株的测试显示，来自用fHbp变体1.1接种的小鼠或成年志愿者的血清对所有亚变体1序列都是杀菌的，然而对最远的序列的滴度低几倍。来自接种疫苗的婴儿的血清对氨基酸变异更敏感，并且与来自给予相同疫苗的成人的血清相比，它们对远距离亚变体1序列具有较低的杀菌活性或没有杀菌活性。使用多组分疫苗可以克服fHbp提供的低覆盖率。我们的结论是，fHbp是一个非常重要的抗原，诱导杀菌抗体的动物，成人和婴儿。然而，鉴于其序列和表达水平的高度可变性，单独的fHbp不太可能在婴儿中提供针对远端氨基酸序列变体的良好保护，因此诱导针对其他抗原的保护性免疫的多组分疫苗更可能在所有年龄组中诱导广泛的保护性免疫。(C)2010爱思唯尔有限公司保留所有权利。
Factor H binding protein (fHbp), one of the main antigens of new vaccines against serogroup B meningococcus, varies in amino acid sequence and level of expression in different clinical isolates. To evaluate the contribution of amino acid sequence variability to vaccine coverage, we constructed a strain that is susceptible to bactericidal killing only by anti-fHbp antibodies and engineered it to express equal levels of 10 different fHbp sub-variants from a constitutive promoter. Testing of these isogenic strains showed that sera from mice or adult volunteers vaccinated with fHbp variant 1.1 were bactericidal against all sub-variants 1 sequences, however the titer against the most distant sequences were several times lower. Sera from vaccinated infants were more susceptible to amino acid variations and they had lower or no bactericidal activity against the distant sub-variants 1 sequences in comparison with sera from adults given the same vaccines. The low coverage provided by fHbp could be overcome using a multicomponent vaccine. We conclude that fHbp is a very important antigen that induces bactericidal antibodies in animals, adults and infants. However, given its high variability of sequence and expression level, it is unlikely that fHbp alone can provide good protection in infants against the distant amino acid sequence variants and therefore multicomponent vaccines inducing protective immunity also against other antigens are more likely to induce a broad protective immunity in all age groups. (C) 2010 Elsevier Ltd. All rights reserved.