A bacterially expressed triple-type chimeric vaccine against human papillomavirus types 51, 69, and 26
A bacterially expressed triple-type chimeric vaccine against human papillomavirus types 51, 69, and 26
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DOI：
10.1016/j.vaccine.2022.09.010
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发表时间：
2022-09-29
期刊：
影响因子：
5.5
通讯作者：
Gu，Ying
中科院分区：
文献类型：
--
作者：
Yu，Miao;Chi，Xin;Gu，Ying
高危型人乳头瘤病毒（HPV）的持续感染是包括宫颈癌在内的一些癌症的主要原因。然而，由于有超过20种致癌HPV类型，很难设计出一种可以提供完整保护的多价疫苗。在这里，我们描述了HPV 51/69/26三型嵌合病毒样颗粒（VLP）的疫苗开发的设计和优化。使用E.大肠杆菌和一系列的N-末端截短策略，我们创建了双和三型嵌合VLPs通过环交换在等效的表面环。主要候选物H69- 51 BC-26 FG具有与其亲本VLP相似的颗粒特性，并且对HPV 51、−69和−26具有相当的免疫原性。当在GMP样设施中生产时，这些H69- 51 BC-26 FG VLP被证实具有用于开发多价HPV疫苗的优异品质。本研究展示了一种适合的方法来创建一个单一的VLP使用类型特异性表位聚类的三型疫苗的设计。
Persistent infection of high-risk human papillomavirus (HPV) is a leading cause of some cancers, including cervical cancer. However, with over 20 carcinogenic HPV types, it is difficult to design a multivalent vaccine that can offer complete protection. Here, we describe the design and optimization of a HPV51/69/26 triple-type chimeric virus-like particle (VLP) for vaccine development. UsingE. coliand a serial N-terminal truncation strategy, we created double- and triple-type chimeric VLPs through loop-swapping at equivalent surface loops. The lead candidate, H69-51BC-26FG, conferred similar particulate properties as that of its parental VLPs and comparable immunogenicity against HPV51, −69 and −26. When produced in a GMP-like facility, these H69-51BC-26FG VLPs were verified to have excellent qualities for the development of a multivalent HPV vaccine. This study showcases an amenable way to create a single VLP using type-specific epitope clustering for the design of a triple-type vaccine.