Development of Neutralizing Monoclonal Antibodies for Oncogenic Human Papillomavirus Types 31, 33, 45, 52, and 58
Development of Neutralizing Monoclonal Antibodies for Oncogenic Human Papillomavirus Types 31, 33, 45, 52, and 58
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DOI：
10.1128/cvi.00773-13
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发表时间：
2014-04-01
影响因子：
--
通讯作者：
Finnefrock, Adam C.
中科院分区：
文献类型：
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作者：
Brown, Martha J.;Seitz, Hanna;Finnefrock, Adam C.
人乳头瘤病毒（HPV）是所有宫颈癌、大量其他肛门生殖器癌以及越来越多的头颈癌的病原体。两种获得许可的疫苗提供对最流行的致癌类型的保护，16和18，负责全球约70%的宫颈癌病例，其中一种还提供对6和11型的保护，负责90%的生殖器疣。疫苗由重组表达的主要衣壳蛋白组成，这些蛋白自组装成病毒样颗粒（VLP）并通过引发中和抗体来预防感染。将其他常见的致癌类型31，33，45，52和58添加到疫苗中将使HPV诱导的癌症的覆盖率增加到约90%。我们描述了针对这五种额外致癌HPV类型的单克隆抗体组的产生和表征，以及高亲和力、类型特异性和公认的构象依赖性中和表位的抗体对的选择。这些特性使得这些抗体成为监测原型疫苗的生产和效力以及监测临床中疫苗诱导的免疫应答的有用工具。
Human papillomavirus (HPV) is the etiological agent for all cervical cancers, a significant number of other anogenital cancers, and a growing number of head and neck cancers. Two licensed vaccines offer protection against the most prevalent oncogenic types, 16 and 18, responsible for approximately 70% of cervical cancer cases worldwide and one of these also offers protection against types 6 and 11, responsible for 90% of genital warts. The vaccines are comprised of recombinantly expressed major capsid proteins that self-assemble into virus-like particles (VLPs) and prevent infection by eliciting neutralizing antibodies. Adding the other frequently identified oncogenic types 31, 33, 45, 52, and 58 to a vaccine would increase the coverage against HPV-induced cancers to approximately 90%. We describe the generation and characterization of panels of monoclonal antibodies to these five additional oncogenic HPV types, and the selection of antibody pairs that were high affinity and type specific and recognized conformation-dependent neutralizing epitopes. Such characteristics make these antibodies useful tools for monitoring the production and potency of a prototype vaccine as well as monitoring vaccine-induced immune responses in the clinic.