Acosta Eliana G, Bartenschlager Ralf
a Department of Infectious Diseases, Molecular Virology , Heidelberg University , Heidelberg , Germany.
b German Center for Infection Research , Heidelberg University , Heidelberg , Germany.
Expert Rev Vaccines. 2016;15(4):467-82. doi: 10.1586/14760584.2016.1121814. Epub 2015 Dec 15.
Highly effective prophylactic vaccines for flaviviruses including yellow fever virus, tick-borne encephalitis virus and Japanese encephalitis virus are currently in use. However, the development of a dengue virus (DENV) vaccine has been hampered by the requirement of simultaneous protection against four distinct serotypes and the threat that DENV-specific antibodies might either mediate neutralization or, on the contrary, exacerbate disease through the phenomenon of antibody-dependent enhancement (ADE) of infection. Therefore, understanding the cellular, biochemical and molecular basis of antibody-mediated neutralization and ADE are fundamental for the development of a safe DENV vaccine. Here we summarize current structural and mechanistic knowledge underlying these phenomena. We also review recent results demonstrating that the humoral immune response triggered during natural DENV infection is able to generate neutralizing antibodies binding complex quaternary epitopes only present on the surface of intact virions.
目前已在使用针对包括黄热病毒、蜱传脑炎病毒和日本脑炎病毒在内的黄病毒的高效预防性疫苗。然而，登革热病毒（DENV）疫苗的研发受到同时抵御四种不同血清型这一要求的阻碍，以及DENV特异性抗体可能介导中和作用，或者相反，通过感染的抗体依赖性增强（ADE）现象加剧疾病的威胁。因此，了解抗体介导的中和作用和ADE的细胞、生化和分子基础对于开发安全的DENV疫苗至关重要。在此，我们总结了这些现象背后当前的结构和机制知识。我们还回顾了近期的研究结果，这些结果表明自然DENV感染期间引发的体液免疫反应能够产生仅结合完整病毒粒子表面存在的复杂四级表位的中和抗体。
