Antigenic Variation of the Dengue Virus 2 Genotypes Impacts the Neutralization Activity of Human Antibodies in Vaccinees.
Antigenic Variation of the Dengue Virus 2 Genotypes Impacts the Neutralization Activity of Human Antibodies in Vaccinees.
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DOI：
10.1016/j.celrep.2020.108226
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发表时间：
2020-10-06
期刊：
影响因子：
8.8
通讯作者：
Baric RS
中科院分区：
文献类型：
--
作者：
Martinez DR;Yount B;Nivarthi U;Munt JE;Delacruz MJ;Whitehead SS;Durbin AP;de Silva AM;Baric RS
登革热病毒(DENV)每年感染全球约3.9亿人。由于四价DENV疫苗对2型DENV(DENV2)有不同的效力，我们评估了DENV2膜前蛋白(PRM)和包膜蛋白(E)的遗传多样性对疫苗性能的影响。我们用代表全球遗传多样性的当代PRM和E分离株产生了一个重组的DENV2基因变异小组。DENV2基因变异体在生长动力学、形态和病毒粒子稳定性方面存在差异。重要的是，DENV2基因变异体被来自DENV2感染者的单抗、多克隆血清中和抗体以及来自TV003 NIH DENV2单价和DENV四价疫苗的疫苗诱导的抗体反应差异地中和。我们的结论是，DENV2、PRM和E基因多样性显著调节抗体中和活性。这些发现对登革热疫苗具有重要意义，登革热疫苗是在病毒型内变异对中和抗体影响最小的假设下开发的。Martinez等人。证明登革2型病毒(DENV2)的基因变异调节感染和疫苗接种的中和抗体活性。这一观察结果强调了基因变异对登革2型病毒逃避体液免疫的影响，建议在设计登革热疫苗时应考虑病毒内型基因变异。
Dengue virus (DENV) infects an estimated 390 million people each year worldwide. As tetravalent DENV vaccines have variable efficacy against DENV serotype 2 (DENV2), we evaluated the role of genetic diversity within the pre-membrane (prM) and envelope (E) proteins of DENV2 on vaccine performance. We generated a recombinant DENV2 genotype variant panel with contemporary prM and E isolates that are representative of global genetic diversity. The DENV2 genotype variants differ in growth kinetics, morphology, and virion stability. Importantly, the DENV2 genotypic variants are differentially neutralized by monoclonal antibodies, polyclonal serum neutralizing antibodies from DENV2-infected human subjects, and vaccine-elicited antibody responses from the TV003 NIH DENV2 monovalent and DENV tetravalent vaccines. We conclude that DENV2 prM and E genetic diversity significantly modulates antibody neutralization activity. These findings have important implications for dengue vaccines, which are being developed under the assumption that intraserotype variation has minimal impact on neutralizing antibodies. Martinez et al. demonstrate that dengue virus serotype 2 (DENV2) genetic variation modulates neutralizing antibody activity from infection and vaccination. This observation underlines that genotypic variation impacts dengue virus 2 evasion from humoral immunity, suggesting that intraserotype genotypic variation should be considered in designing dengue vaccines.
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DOI：
10.1126/science.aaa8651
发表时间：
2015-07-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fibriansah G;Ibarra KD;Ng TS;Smith SA;Tan JL;Lim XN;Ooi JS;Kostyuchenko VA;Wang J;de Silva AM;Harris E;Crowe JE Jr;Lok SM
通讯作者：
Lok SM
影响因子：
6.4
作者：
Kirkpatrick, Beth D.;Durbin, Anna P.;Whitehead, Steven S.
通讯作者：
Whitehead, Steven S.
影响因子：
3.7
作者：
Durbin, Anna P.;Mayer, Sandra V.;Vasilakis, Nikos
通讯作者：
Vasilakis, Nikos
影响因子：
3.8
作者：
Forshey, Brett M.;Reiner, Robert C.;Stoddard, Steven T.
通讯作者：
Stoddard, Steven T.
影响因子：
158.5
作者：
Hadinegoro, S. R.;Arredondo-Garcia, J. L.;Saville, M.
通讯作者：
Saville, M.