Olczak Pola, Roden Richard B S
Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
Department of Oncology, The Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
Vaccines (Basel). 2020 Oct 1;8(4):568. doi: 10.3390/vaccines8040568.
The human papillomaviruses (HPVs) are a family of small DNA tumor viruses including over 200 genotypes classified by phylogeny into several genera. Different genera of HPVs cause ano-genital and oropharyngeal cancers, skin cancers, as well as benign diseases including skin and genital warts. Licensed vaccines composed of L1 virus-like particles (VLPs) confer protection generally restricted to the ≤9 HPV types targeted. Here, we examine approaches aimed at broadening the protection against diverse HPV types by targeting conserved epitopes of the minor capsid protein, L2. Compared to L1 VLP, L2 is less immunogenic. However, with appropriate presentation to the immune system, L2 can elicit durable, broadly cross-neutralizing antibody responses and protection against skin and genital challenge with diverse HPV types. Such approaches to enhance the strength and breadth of the humoral response include the display of L2 peptides on VLPs or viral capsids, bacteria, thioredoxin and other platforms for multimerization. Neither L2 nor L1 vaccinations elicit a therapeutic response. However, fusion of L2 with early viral antigens has the potential to elicit both prophylactic and therapeutic immunity. This review of cross-protective HPV vaccines based on L2 is timely as several candidates have recently entered early-phase clinical trials.
人乳头瘤病毒（HPV）是一类小型DNA肿瘤病毒，包括200多种基因型，根据系统发育分类为几个属。不同属的HPV会引发肛门生殖器癌和口咽癌、皮肤癌以及包括皮肤和生殖器疣在内的良性疾病。由L1病毒样颗粒（VLP）组成的获批疫苗所提供的保护通常仅限于所针对的≤9种HPV类型。在此，我们研究旨在通过靶向次要衣壳蛋白L2的保守表位来扩大针对多种HPV类型的保护范围的方法。与L1 VLP相比，L2的免疫原性较低。然而，通过适当地呈现给免疫系统，L2可以引发持久的、广泛交叉中和的抗体反应，并提供针对多种HPV类型的皮肤和生殖器攻击的保护。此类增强体液反应强度和广度的方法包括在VLP或病毒衣壳、细菌、硫氧还蛋白和其他多聚化平台上展示L2肽。L2和L1疫苗接种均不会引发治疗反应。然而，将L2与早期病毒抗原融合有可能引发预防和治疗性免疫。鉴于最近有几种候选疫苗已进入早期临床试验阶段，此次对基于L2的交叉保护性HPV疫苗的综述很及时。
