Department of Pathology, University of Cambridge, Cambridge, UK.
Curr Opin Infect Dis. 2010 Feb;23(1):70-5. doi: 10.1097/QCO.0b013e328334c0e1.
Prophylactic human papillomavirus (HPV) L1 virus like particle (VLP) vaccines have been shown, in large randomized controlled clinical trials, to be very immunogenic, well tolerated and highly efficacious against ano-genital disease caused by the vaccine HPV types. However, these vaccines, at the present, protect against only two of the 15 oncogenic genital HPV types, they are expensive, delivered by intramuscular injection and require a cold chain.
The challenges are to develop cheap, thermostable vaccines that can be delivered by noninjectable methods that provide long-term (decades) protection at mucosal surfaces to most, if not all, oncogenic HPV types that is as good as the current VLP vaccines. Polyvalent VLP vaccines covering several oncogenic types are in clinical trials. The most promising of the non-VLP second generation vaccines include L1 capsomers and L2 protein and peptides, suitably adjuvanted. Recent data on the mechanism of viral entry and the dynamics of the interaction of the viral capsid proteins L1 and L2 with the cell surface provide a rationale for the protection offered by these new approaches.
These second generation vaccines are immunogenic and can provide broad protection but are either at early stage in clinical trial or not in trials. The current VLP prophylactic vaccines are likely to be the only option for the coming decade.
在大规模随机对照临床试验中，预防性人乳头瘤病毒（HPV）L1 病毒样颗粒（VLP）疫苗具有很强的免疫原性、良好的耐受性和针对疫苗 HPV 型引起的肛门生殖器疾病的高度有效性。然而，这些疫苗目前仅能预防 15 种致癌性生殖器 HPV 型中的两种，价格昂贵，通过肌肉注射给药，且需要冷链。
目前的挑战是开发廉价、耐热的疫苗，通过非注射方法给药，在粘膜表面提供对大多数（如果不是全部）致癌 HPV 型的长期（数十年）保护，其效果与当前的 VLP 疫苗相当。涵盖多种致癌类型的多价 VLP 疫苗正在临床试验中。最有前途的第二代非 VLP 疫苗包括 L1 衣壳蛋白和 L2 蛋白和肽，并适当佐剂化。最近关于病毒进入机制和病毒衣壳蛋白 L1 和 L2 与细胞表面相互作用动力学的数据为这些新方法提供的保护提供了依据。
这些第二代疫苗具有免疫原性，可以提供广泛的保护，但要么处于临床试验的早期阶段，要么尚未进行临床试验。目前的预防性 VLP 疫苗可能是未来十年的唯一选择。
