Antibody-Based Strategies to Prevent and Treat Influenza.
Antibody-Based Strategies to Prevent and Treat Influenza.
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DOI：
10.3389/fimmu.2015.00315
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发表时间：
2015
影响因子：
7.3
通讯作者：
Sasisekharan R
中科院分区：
文献类型：
--
作者：
Shriver Z;Trevejo JM;Sasisekharan R
使用抗体的被动免疫是其他抗病毒治疗方案的一个有希望的替代方案。单次注射抗体产生季节性保护的潜力很有吸引力，并已对许多传染性病原体进行了研究。然而，直到最近，基于抗体的对抗感染因子的策略一直受到阻碍，因为大多数抗体已被发现是菌株特异性的，在许多情况下病毒进化出耐药性。流感病毒、登革热病毒和艾滋病毒中广泛中和抗体（bNAbs）的发现，结合多种结构多样的毒株，重新引起了人们对这一领域的兴趣。本综述将重点关注发现bNAbs的新技术、免疫疗法作为现有抗病毒疗法重要补充的挑战和机遇，以及抗体发现在合理发现疫苗中的作用——特别是针对流感的药物。多种候选抗体已经进入临床，并提高了单一抗体或抗体的小组合可以有效中和多种菌株的可能性。然而，挑战依然存在，包括对抗逃逸变异、抗体分布的药效学以及超越病毒学终点的有效性生物标志物的开发。
Passive immunization using antibodies is a promising alternative to other antiviral treatment options. The potential for seasonal protection arising from a single injection of antibodies is appealing and has been pursued for a number of infectious agents. However, until recently, antibody-based strategies to combat infectious agents have been hampered due to the fact that most antibodies have been found to be strain specific, with the virus evolving resistance in many cases. The discovery of broadly neutralizing antibodies (bNAbs) in influenza, dengue virus, and HIV, which bind to multiple, structurally diverse strains, has provided renewed interest in this area. This review will focus on new technologies that enable the discovery of bNAbs, the challenges and opportunities of immunotherapies as an important addition to existing antiviral therapy, and the role of antibody discovery in informing rational vaccine discovery – with agents targeting influenza specifically addressed. Multiple candidates have entered the clinic and raise the possibility that a single antibody or small combination of antibodies can effectively neutralize a wide variety of strains. However, challenges remain – including combating escape variants, pharmacodynamics of antibody distribution, and development of efficacy biomarkers beyond virologic endpoints.