Antibody Recognition of the Dengue Virus Proteome and Implications for Development of Vaccines
Antibody Recognition of the Dengue Virus Proteome and Implications for Development of Vaccines
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DOI：
10.1128/cvi.00016-11
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发表时间：
2011-04-01
影响因子：
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通讯作者：
Ulrich, Robert G.
中科院分区：
文献类型：
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作者：
Fernandez, Stefan;Cisney, Emily D.;Ulrich, Robert G.
登革热是由四种不同血清型的登革热病毒引起的蚊媒感染，每种血清型都周期性地出现在沿着赤道的热带和亚热带地区。虽然疫苗目前正在开发中，但没有一种可供普通人群使用。这些疫苗成功发展的主要障碍之一是缺乏明确的免疫保护相关物。在这里，我们描述了一种蛋白质微阵列方法，用于测量抗体对完整病毒蛋白质组的反应，该蛋白质组由所有四种登革热病毒血清型（1至4）的结构（衣壳、膜和包膜）和非结构（NS 1、NS 2A、NS 2B、NS 3、NS 4A、NS 4 B和NS 5）组分组成。我们研究了恒河猴接种四价疫苗组成的减毒活病毒（LAV）或纯化的灭活病毒（PIV），然后加强与LAV和挑战野生型登革病毒。我们检测到时间增加的抗体对包膜蛋白的反应，无论是疫苗，而只有PIV/LAV疫苗接种策略导致抗衣壳抗体。与疫苗接种的结果相反，用每种血清型的野生型病毒攻击的幼稚猕猴表现出对非结构和结构组分的平衡应答，包括对膜蛋白的应答。我们的研究结果表明，区分细节的性质抗体反应登革热病毒在蛋白质组水平，并建议疫苗开发的有用性，这些信息。
Dengue is a mosquito-borne infection caused by four distinct serotypes of dengue virus, each appearing cyclically in the tropics and subtropics along the equator. Although vaccines are currently under development, none are available to the general population. One of the main impediments to the successful advancement of these vaccines is the lack of well-defined immune correlates of protection. Here, we describe a protein microarray approach for measuring antibody responses to the complete viral proteome comprised of the structural (capsid, membrane, and envelope) and nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) components of all four dengue virus serotypes (1 to 4). We examined rhesus macaques vaccinated with tetravalent vaccines consisting of live-attenuated virus (LAV) or purified inactivated virus (PIV), followed by boosting with LAV and challenging with wild-type dengue virus. We detected temporal increases in antibodies against envelope proteins in response to either vaccine, while only the PIV/LAV vaccination strategy resulted in anticapsid antibodies. In contrast to results from vaccination, naive macaques challenged with wild-type viruses of each serotype demonstrated a balanced response to nonstructural and structural components, including responses against the membrane protein. Our results demonstrate discriminating details concerning the nature of antibody responses to dengue virus at the proteomic level and suggest the usefulness of this information for vaccine development.