Huber Bettina, Wang Joshua Weiyuan, Roden Richard B S, Kirnbauer Reinhard
Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria.
Department of Pathology, The Johns Hopkins University, Baltimore, MD 21218, USA.
J Clin Med. 2021 Mar 3;10(5):1044. doi: 10.3390/jcm10051044.
Licensed human papillomavirus (HPV) vaccines contain virus-like particles (VLPs) self-assembled from L1 major-capsid proteins that are remarkably effective prophylactic immunogens. However, the induced type-restricted immune response limits coverage to the included vaccine types, and costly multiplex formulations, restrictive storage and distribution conditions drive the need for next generation HPV vaccines. Vaccine candidates based upon the minor structural protein L2 are particularly promising because conserved N-terminal epitopes induce broadly cross-type neutralizing and protective antibodies. Several strategies to increase the immunological potency of such epitopes are being investigated, including concatemeric multimers, fusion to toll-like receptors ligands or T cell epitopes, as well as immunodominant presentation by different nanoparticle or VLP structures. Several promising L2-based vaccine candidates have reached or will soon enter first-in-man clinical studies. RG1-VLP present the HPV16L2 amino-acid 17-36 conserved neutralization epitope "RG1" repetitively and closely spaced on an immunodominant surface loop of HPV16 L1-VLP and small animal immunizations provide cross-protection against challenge with all medically-significant high-risk and several low-risk HPV types. With a successful current good manufacturing practice (cGMP) campaign and this promising breadth of activity, even encompassing cross-neutralization of several cutaneous HPV types, RG1-VLP are ready for a first-in-human clinical study. This review aims to provide a general overview of these candidates with a special focus on the RG1-VLP vaccine and its road to the clinic.
获得许可的人乳头瘤病毒（HPV）疫苗含有由L1主要衣壳蛋白自组装而成的病毒样颗粒（VLP），这些病毒样颗粒是非常有效的预防性免疫原。然而，诱导的型特异性免疫反应将疫苗覆盖范围限制在所包含的疫苗类型上，并且昂贵的多价配方、严格的储存和分发条件促使人们需要新一代HPV疫苗。基于次要结构蛋白L2的候选疫苗特别有前景，因为保守的N端表位可诱导广泛的交叉型中和抗体和保护性抗体。目前正在研究几种提高此类表位免疫效力的策略，包括串联多聚体、与Toll样受体配体或T细胞表位融合，以及通过不同的纳米颗粒或VLP结构进行免疫显性呈递。几种有前景的基于L2的候选疫苗已经或即将进入首次人体临床研究。RG1-VLP在HPV16 L1-VLP的免疫显性表面环上重复且紧密间隔地呈现HPV16L2氨基酸17-36保守中和表位“RG1”，对小动物的免疫接种可提供针对所有具有医学意义的高危和几种低危HPV类型攻击的交叉保护。凭借当前成功的药品生产质量管理规范（cGMP）活动以及这种有前景的广泛活性，甚至包括对几种皮肤HPV类型的交叉中和作用，RG1-VLP已准备好进行首次人体临床研究。本综述旨在对这些候选疫苗进行总体概述，特别关注RG1-VLP疫苗及其临床之路。
