Humoral immune responses of dengue fever patients using epitope-specific serotype-2 virus-like particle antigens.
Humoral immune responses of dengue fever patients using epitope-specific serotype-2 virus-like particle antigens.
复制标题
DOI：
10.1371/journal.pone.0004991
复制
发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Chang GJ
中科院分区：
文献类型：
--
作者：
Crill WD;Hughes HR;Delorey MJ;Chang GJ
登革病毒（DENV）是一种严重的蚊媒病原体，造成重大的全球性疾病负担，无论是经典的登革热（DF）还是其最严重的表现登革出血热（DHF）。世界上近一半的人口面临登革热疾病的风险，估计每年有数百万人感染;随着蚊子媒介的不断扩大和登革热/登革出血热的流行，这种情况将继续恶化。目前，还没有获得许可的登革热疫苗或抗病毒药物，尽管30多年来一直致力于开发安全有效的登革热疫苗。有希望的候选疫苗正处于开发和测试阶段，但需要更好地了解对DENV感染和疫苗接种的免疫反应。对DENV感染的体液免疫应答是复杂的，并且可能加剧致病性，但对于免疫保护是必不可少的。在这份报告中，我们开发了DENV-2包膜（E）蛋白表位特异性抗原，并测量了免疫球蛋白对DENV-2感染的人血清样品中三种不同表位的反应。对DENV-2感染的免疫球蛋白反应表现出显着的个体差异。以结构域II中的融合肽为中心的广泛交叉反应性表位为目标的抗体群体较大，高度可变，并且在原发性DENV-2感染血清中比在继发性DENV-2感染血清中更大。E蛋白结构域III交叉反应性免疫球蛋白群体也类似地可变，并且在IgM中比在IgG中大得多。DENV-2特异性结构域III IgG形成非常小比例的抗体应答，但与DENV-2中和显著相关，表明在鼠研究中识别该表位的高度保护性IgG也在人中起作用。该报告开始梳理对DENV感染的复杂体液免疫应答，因此对于提高我们对登革热疾病和保护的免疫学相关性的理解，与DENV疫苗开发和测试相关，非常重要。
Dengue virus (DENV) is a serious mosquito-borne pathogen causing significant global disease burden, either as classic dengue fever (DF) or in its most severe manifestation dengue hemorrhagic fever (DHF). Nearly half of the world's population is at risk of dengue disease and there are estimated to be millions of infections annually; a situation which will continue to worsen with increasing expansion of the mosquito vectors and epidemic DF/DHF. Currently there are no available licensed vaccines or antivirals for dengue, although significant effort has been directed toward the development of safe and efficacious dengue vaccines for over 30 years. Promising vaccine candidates are in development and testing phases, but a better understanding of immune responses to DENV infection and vaccination is needed. Humoral immune responses to DENV infection are complex and may exacerbate pathogenicity, yet are essential for immune protection. In this report, we develop DENV-2 envelope (E) protein epitope-specific antigens and measure immunoglobulin responses to three distinct epitopes in DENV-2 infected human serum samples. Immunoglobulin responses to DENV-2 infection exhibited significant levels of individual variation. Antibody populations targeting broadly cross-reactive epitopes centered on the fusion peptide in structural domain II were large, highly variable, and greater in primary than in secondary DENV-2 infected sera. E protein domain III cross-reactive immunoglobulin populations were similarly variable and much larger in IgM than in IgG. DENV-2 specific domain III IgG formed a very small proportion of the antibody response yet was significantly correlated with DENV-2 neutralization, suggesting that the highly protective IgG recognizing this epitope in murine studies plays a role in humans as well. This report begins to tease apart complex humoral immune responses to DENV infection and is thus important for improving our understanding of dengue disease and immunological correlates of protection, relevant to DENV vaccine development and testing.
登录
查看更多内容
DOI：
10.1073/pnas.0703498104
发表时间：
2007-05-29
影响因子：
11.1
作者：
Goncalvez, Ana P.;Engle, Ronald E.;Lai, Ching-Juh
通讯作者：
Lai, Ching-Juh
影响因子：
5.4
作者：
Chang, GJJ;Hunt, AR;Davis, B
通讯作者：
Davis, B
影响因子：
--
作者：
Chiou, Shyan-Song;Crill, Wayne D.;Chang, Gwong-Jen J.
通讯作者：
Chang, Gwong-Jen J.
影响因子：
11.8
作者：
Guzman MG;Alvarez M;Rodriguez-Roche R;Bernardo L;Montes T;Vazquez S;Morier L;Alvarez A;Gould EA;Kouri G;Halstead SB
通讯作者：
Halstead SB
影响因子：
5.4
作者：
Crill, WD;Chang, GJJ
通讯作者：
Chang, GJJ