The global distribution and diversity of protein vaccine candidate antigens in the highly virulent Streptococcus pnuemoniae serotype 1.
The global distribution and diversity of protein vaccine candidate antigens in the highly virulent Streptococcus pnuemoniae serotype 1.
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DOI：
10.1016/j.vaccine.2016.12.037
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发表时间：
2017-02-07
期刊：
影响因子：
5.5
通讯作者：
PAGe consortium
中科院分区：
文献类型：
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作者：
Cornick JE;Tastan Bishop Ö;Yalcin F;Kiran AM;Kumwenda B;Chaguza C;Govindpershad S;Ousmane S;Senghore M;du Plessis M;Pluschke G;Ebruke C;McGee L;Sigaùque B;Collard JM;Bentley SD;Kadioglu A;Antonio M;von Gottberg A;French N;Klugman KP;Heyderman RS;Alderson M;Everett DB;PAGe consortium
血清型1是全球肺炎球菌疾病最常见的病因之一。目前正在开发肺炎球菌蛋白疫苗，作为肺炎球菌结合疫苗的替代干预策略。有效的肺炎球菌蛋白疫苗的先决条件是靶抗原在肺炎球菌群体中普遍存在且变异最小，并且能够诱导强烈的人体免疫反应。我们使用计算机分析评估了来自四大洲26个不同国家的445例血清1型肺炎球菌中七种候选蛋白疫苗（CbpA、PcpA、PhtD、PspA、SP0148、SP1912、SP2108）的流行情况。CbpA (76%), PspA (68%), PhtD (28%), PcpA（11%）在研究人群中没有普遍编码，并且不能提供针对血清型1的完全覆盖。PcpA广泛存在于欧洲人群中（82%），但不存在于非洲人群中（2%）。一种含有CbpA、PcpA、PhtD和PspA的多价疫苗预计可覆盖全球86%的人口。SP0148、SP1912和SP2108被普遍编码，我们进一步评估了它们的预测氨基酸、抗原和结构变异。鉴定出这些蛋白的多个等位变异，不同的等位变异在不同的大陆占主导地位；预计观察到的变异会影响2个SP0148变异、1个SP1912变异和4个SP2108变异的抗原性和结构，但这些变异只存在于全球人口的一小部分（<2%）。绝大多数观察到的变异预计对含有肺炎链球菌TIGR4 SP0148、SP1912和/或SP2108单一变异的蛋白质疫苗的有效性没有影响。我们的研究结果强调了在设计全球疫苗干预措施时考虑地理差异的重要性，并支持继续开发SP0148、SP1912和SP2108作为针对这一重要肺炎球菌血清型的蛋白候选疫苗。
Serotype 1 is one of the most common causes of pneumococcal disease worldwide. Pneumococcal protein vaccines are currently being developed as an alternate intervention strategy to pneumococcal conjugate vaccines. Pre-requisites for an efficacious pneumococcal protein vaccine are universal presence and minimal variation of the target antigen in the pneumococcal population, and the capability to induce a robust human immune response. We used in silico analysis to assess the prevalence of seven protein vaccine candidates (CbpA, PcpA, PhtD, PspA, SP0148, SP1912, SP2108) among 445 serotype 1 pneumococci from 26 different countries, across four continents. CbpA (76%), PspA (68%), PhtD (28%), PcpA (11%) were not universally encoded in the study population, and would not provide full coverage against serotype 1. PcpA was widely present in the European (82%), but not in the African (2%) population. A multi-valent vaccine incorporating CbpA, PcpA, PhtD and PspA was predicted to provide coverage against 86% of the global population. SP0148, SP1912 and SP2108 were universally encoded and we further assessed their predicted amino acid, antigenic and structural variation. Multiple allelic variants of these proteins were identified, different allelic variants dominated in different continents; the observed variation was predicted to impact the antigenicity and structure of two SP0148 variants, one SP1912 variant and four SP2108 variants, however these variants were each only present in a small fraction of the global population (<2%). The vast majority of the observed variation was predicted to have no impact on the efficaciousness of a protein vaccine incorporating a single variant of SP0148, SP1912 and/or SP2108 from S. pneumoniae TIGR4. Our findings emphasise the importance of taking geographic differences into account when designing global vaccine interventions and support the continued development of SP0148, SP1912 and SP2108 as protein vaccine candidates against this important pneumococcal serotype.