Kiamba Eunice Wavinya, Goodier Martin R, Clarke Ed
Vaccines and Immunity Theme, MRC Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, Gambia.
Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Front Immunol. 2025 Jun 16;16:1591297. doi: 10.3389/fimmu.2025.1591297. eCollection 2025.
Human papillomavirus (HPV) is the most common sexually transmitted infection. About 90% of HPV infections are transient, resolving without any need for intervention. Most of HPV infections are low-risk non-oncogenic. However, persistent infection with high-risk oncogenic HPV types is the cause of cervical as well as various other anogenital and oropharyngeal cancers. HPV infection on either cutaneous or mucosal surfaces activates both innate and adaptive antiviral immune cells including Langerhans and keratinocyte cells, natural killer cells, B and T cells. These cellular responses alongside their corresponding cytokine profiles have been associated with clearance of HPV infection and regression of HPV associated disease although the actual immune mechanisms involved are not well understood. Current HPV vaccines are based on self -assembled virus-like particles (VLP) from the major viral capsid protein and target the high-risk HPV types as well as two low-risk types responsible for genital warts. The vaccines generate antibody protection against new infections with no effect on already established infections and HPV-associated diseases. Certainly, despite the high effectiveness of current prophylactic HPV vaccines, therapeutic HPV vaccines are needed for treatment of already established HPV infections and disease. Although there have been great efforts in development of therapeutic vaccines, none is yet to be licensed due to low efficacy and safety concerns. There is therefore a need to understand both natural and vaccine-induced immunity, for development of effective and safe therapeutic HPV vaccines. Additionally, a better understanding of the immunogenicity of HPV vaccines, which are among the best subunit vaccines developed to date, may identify immune pathways that could be targeted for development of similarly effective vaccines for other diseases. This review summarises available literature on immune responses to both HPV infection and vaccination, with an aim of improving overall understanding on this subject. This may provide insights for better targeting of both therapeutic and prophylactic vaccines, not only for HPV but also other antigen targets.
人乳头瘤病毒（HPV）是最常见的性传播感染病原体。约90%的HPV感染是短暂性的，无需任何干预即可自行消退。大多数HPV感染为低风险、非致癌性的。然而，持续感染高危致癌性HPV类型是导致宫颈癌以及其他各种肛门生殖器和口咽癌的原因。HPV在皮肤或黏膜表面的感染会激活先天性和适应性抗病毒免疫细胞，包括朗格汉斯细胞和角质形成细胞、自然杀伤细胞、B细胞和T细胞。尽管其中涉及的实际免疫机制尚未完全了解，但这些细胞反应及其相应的细胞因子谱与HPV感染的清除以及HPV相关疾病的消退有关。目前的HPV疫苗是基于主要病毒衣壳蛋白自组装而成的病毒样颗粒（VLP），针对高危HPV类型以及导致尖锐湿疣的两种低危类型。这些疫苗可产生抗体保护作用，预防新的感染，但对已有的感染和HPV相关疾病无效。当然，尽管目前的预防性HPV疫苗具有很高的有效性，但仍需要治疗性HPV疫苗来治疗已有的HPV感染和疾病。尽管在治疗性疫苗的研发方面付出了巨大努力，但由于疗效不佳和安全性问题，尚无一种获得许可。因此，有必要了解天然免疫和疫苗诱导免疫，以开发有效且安全的治疗性HPV疫苗。此外，更好地理解HPV疫苗的免疫原性（HPV疫苗是迄今为止研发的最佳亚单位疫苗之一），可能会确定可作为靶点的免疫途径，用于开发针对其他疾病的类似有效疫苗。本综述总结了关于HPV感染和疫苗接种免疫反应的现有文献，旨在提高对该主题的整体认识。这可能为更好地靶向治疗性和预防性疫苗提供见解，不仅适用于HPV，也适用于其他抗原靶点。
