State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361102, China.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen 361102, China; The Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, Xiamen University, Xiamen 361102, China.
Vaccine. 2022 Oct 6;40(42):6141-6152. doi: 10.1016/j.vaccine.2022.09.010. Epub 2022 Sep 16.
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. Using E. coli and 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.
高危型人乳头瘤病毒（HPV）持续感染是某些癌症（包括宫颈癌）的主要病因。然而，由于致癌性 HPV 类型超过 20 种，因此很难设计出能够提供完全保护的多价疫苗。在这里，我们描述了 HPV51/69/26 三型嵌合病毒样颗粒（VLP）的设计和优化，用于疫苗开发。我们使用大肠杆菌和串联 N 端截断策略，通过在等效表面环处进行环交换，构建了双型和三型嵌合 VLP。候选物 H69-51BC-26FG 与亲本 VLPs 具有相似的颗粒特性，对 HPV51、-69 和 -26 具有相当的免疫原性。在类似 GMP 的设施中生产时，这些 H69-51BC-26FG VLP 具有出色的质量，可用于开发多价 HPV 疫苗。这项研究展示了一种通过使用针对三型疫苗设计的特定型别表位聚类来创建单 VLP 的可行方法。
