Application of a Neisseria meningitidis antigen microarray to identify candidate vaccine proteins from a human Phase I clinical trial
Application of a Neisseria meningitidis antigen microarray to identify candidate vaccine proteins from a human Phase I clinical trial
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DOI：
10.1016/j.vaccine.2022.05.032
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发表时间：
2022-06-10
期刊：
影响因子：
5.5
通讯作者：
Derrick, Jeremy P.
中科院分区：
文献类型：
--
作者：
Chang, Chun-Mien;Awanye, Amaka M.;Derrick, Jeremy P.
脑膜炎双球菌脑膜炎是一种罕见但严重的疾病，主要影响儿童和年轻人。脑膜炎奈瑟氏菌的外膜囊泡(OMV)已成功地用作疫苗预防这种疾病，尽管它们只对现有的许多变种中的有限数量提供保护。已经有许多尝试寻找合适的蛋白质抗原，用于提供对疾病的广泛保护的已定义疫苗，例如导致开发四组分4CMenB疫苗的尝试。我们之前曾报道，作为I期临床试验的一部分，我们使用蛋白质抗原微阵列来筛选OMV疫苗接受者血清中的免疫球蛋白抗体。在这里，我们展示了计算方法可以用来聚集在同一个体中引起相似反应的抗原。将免疫球蛋白抗体结合数据与4,005个线性回归进行拟合，确定了表现出显著相关性的抗原对。有些来自不同第四纪状态的相同抗原，而另一些可能出于功能或免疫学原因而相关。我们还进行了统计分析，以检查个体血清杀菌抗体(SBA)滴度和针对特定抗原的IgG反应性之间的相关性。Kendall的tau和Spearman的等级相关系数统计在五个不同的分离株中识别出与LOG(SBA)滴度相关的特定抗原。已鉴定的主要抗原为PorA和PorB、RmpM、OPCA，以及IV型毛发装配分泌素PiIQ。其他已鉴定的次要抗原包括一种脂蛋白、两种来自BAM复合体和外流通道MTRE的蛋白。我们的结果表明，考虑到整个抗原组成，并考虑到抗原之间的潜在相互作用，在设计未来的脑膜炎双球菌疫苗时可能有价值。这种方法的优点是，它使用来自人类而不是动物免疫的数据，并且它避免了对单个抗原进行筛选的需要。(C)2022年提交人。爱思唯尔有限公司出版。
Meningococcal meningitis is a rare but serious condition affecting mainly children and young adults. Outer membrane vesicles (OMV) from Neisseria meningitidis have been used successfully as vaccines against the disease, although they only provide protection against a limited number of the many existing variants. There have been many attempts to identify suitable protein antigens for use in defined vaccines that provide broad protection against the disease, such as that leading to the development of the four component 4CMenB vaccine. We previously reported the use of a protein antigen microarray to screen for IgG antibodies in sera derived from human recipients of an OMV-based vaccine, as part of a Phase I clinical trial. Here, we show that computational methods can be used to cluster antigens that elicit similar responses in the same individuals. Fitting of IgG antibody binding data to 4,005 linear regressions identified pairs of antigens that exhibited significant correlations. Some were from the same antigens in different quaternary states, whilst others might be correlated for functional or immunological reasons. We also conducted statistical analyses to examine correlations between individual serum bactericidal antibody (SBA) titres and IgG reactivity against specific antigens. Both Kendall's tau and Spearman's rank correlation coefficient statistics identified specific antigens that correlated with log(SBA) titre in five different isolates. The principal antigens identified were PorA and PorB, RmpM, OpcA, and the type IV pilus assembly secretin, PiIQ. Other minor antigens identified included a lipoprotein, two proteins from the BAM complex and the efflux channel MtrE. Our results suggest that consideration of the entire antigen composition, and allowance for potential interaction between antigens, could be valuable in designing future meningococcal vaccines. Such an approach has the advantages that it uses data derived from human, rather than animal, immunization and that it avoids the need to screen individual antigens. (C) 2022 The Authors. Published by Elsevier Ltd.