Qualitative and quantitative assessment of meningococcal antigens to evaluate the potential strain coverage of protein-based vaccines
Qualitative and quantitative assessment of meningococcal antigens to evaluate the potential strain coverage of protein-based vaccines
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DOI：
10.1073/pnas.1013758107
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发表时间：
2010-11-09
影响因子：
11.1
通讯作者：
Giuliani, Marzia Monica
中科院分区：
文献类型：
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作者：
Donnelly, John;Medini, Duccio;Giuliani, Marzia Monica
一种独特的针对B群脑膜炎双球菌的多组分疫苗融合了新的基因组衍生蛋白fHBP、NHBA和NADA，这些蛋白在序列和表达水平上可能会有所不同。使用公认的预防侵袭性脑膜炎双球菌疾病的相关性来衡量这种疫苗的有效性，可能需要对每个地理区域的许多不同菌株进行血清杀菌试验(SBA)。这种方法是不切实际的，特别是对于血清容量非常有限的婴儿。为了解决这一问题，我们开发了脑膜炎双球菌抗原分型系统(MATS)，该系统将独特的疫苗抗原特异性ELISA与PORA基因分型信息相结合，检测抗原的定性和定量差异。ELISA与SBA对菌株的杀灭相关，并测量免疫交叉反应和抗原NHBA、NADA和fHBP的数量。我们发现，对于三种疫苗抗原中的任何一种，在ELISA中超过阈值的菌株被SBA中的免疫血清杀死的概率为80%。对两种或两种以上抗原阳性的菌株有96%的致死概率。在疫苗中加入多个不同的抗原可提高覆盖范围，并防止在一个抗原发生突变或丢失时失去覆盖范围。一项简单而高通量的检测与杀菌活性相关的发现是脑膜炎球菌疫苗开发的一个里程碑。这种检测方法可以对大量菌株进行分型，并预测以蛋白质为基础的脑膜炎双球菌疫苗的覆盖率。类似的检测方法也可用于以蛋白质为基础的疫苗，以对抗其他细菌。
A unique multicomponent vaccine against serogroup B meningococci incorporates the novel genome-derived proteins fHbp, NHBA, and NadA that may vary in sequence and level of expression. Measuring the effectiveness of such vaccines, using the accepted correlate of protection against invasive meningococcal disease, could require performing the serum bactericidal assay (SBA) against many diverse strains for each geographic region. This approach is impractical, especially for infants, where serum volumes are very limited. To address this, we developed the meningococcal antigen typing system (MATS) by combining a unique vaccine antigen-specific ELISA, which detects qualitative and quantitative differences in antigens, with PorA genotyping information. The ELISA correlates with killing of strains by SBA and measures both immunologic cross-reactivity and quantity of the antigens NHBA, NadA, and fHbp. We found that strains exceeding a threshold value in the ELISA for any of the three vaccine antigens had >= 80% probability of being killed by immune serum in the SBA. Strains positive for two or more antigens had a 96% probability of being killed. Inclusion of multiple different antigens in the vaccine improves breadth of coverage and prevents loss of coverage if one antigen mutates or is lost. The finding that a simple and high-throughput assay correlates with bactericidal activity is a milestone in meningococcal vaccine development. This assay allows typing of large panels of strains and prediction of coverage of protein-based meningococcal vaccines. Similar assays may be used for protein-based vaccines against other bacteria.