Laboratory of Virology, "Lazzaro Spallanzani" National Institute for Infectious Diseases, IRCCS, Rome, Italy.
Department of Biology and Biotechnology "C. Darwin," Sapienza University, Rome, Italy.
Front Immunol. 2020 Feb 18;11:188. doi: 10.3389/fimmu.2020.00188. eCollection 2020.
Human papillomavirus (HPV) is the most common sexually transmitted virus. The high-risk HPV types (i.e., HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) are considered to be the main etiological agents of genital tract cancers, such as cervical, vulvar, vaginal, penile, and anal cancers, and of a subset of head and neck cancers. Three prophylactic HPV vaccines are available that are bivalent (vs. HPV16, 18), tetravalent (vs. HPV6, 11, 16, 18), and non-avalent (vs. HPV6, 11, 16, 18, 31, 33,45, 52, 58). All of these vaccines are based on recombinant DNA technology, and they are prepared from the purified L1 protein that self-assembles to form the HPV type-specific empty shells (i.e., virus-like particles). These vaccines are highly immunogenic and induce specific antibodies. Therapeutic vaccines differ from prophylactic vaccines, as they are designed to generate cell-mediated immunity against transformed cells, rather than neutralizing antibodies. Among the HPV proteins, the E6 and E7 oncoproteins are considered almost ideal as targets for immunotherapy of cervical cancer, as they are essential for the onset and evolution of malignancy and are constitutively expressed in both premalignant and invasive lesions. Several strategies have been investigated for HPV therapeutic vaccines designed to enhance CD4 and CD8 T-cell responses, including genetic vaccines (i.e., DNA/ RNA/virus/ bacterial), and protein-based, peptide-based or dendritic-cell-based vaccines. However, no vaccine has yet been licensed for therapeutic use. Several studies have suggested that administration of prophylactic vaccines immediately after surgical treatment of CIN2 cervical lesions can be considered as an adjuvant to prevent reactivation or reinfection, and other studies have described the relevance of prophylactic vaccines in the management of genital warts. This review summarizes the leading features of therapeutic vaccines, which mainly target the early oncoproteins E6 and E7, and prophylactic vaccines, which are based on the L1 capsid protein. Through an analysis of the specific immunogenic properties of these two types of vaccines, we discuss why and how prophylactic vaccines can be effective in the treatment of HPV-related lesions and relapse.
人乳头瘤病毒（HPV）是最常见的性传播病毒。高危型 HPV 类型（即 HPV16、18、31、33、35、39、45、51、52、56、58、59）被认为是生殖道癌症（如宫颈癌、外阴癌、阴道癌、阴茎癌和肛门癌）和一部分头颈部癌症的主要病因。目前有三种预防性 HPV 疫苗，分别为二价疫苗（针对 HPV16、18）、四价疫苗（针对 HPV6、11、16、18）和非四价疫苗（针对 HPV6、11、16、18、31、33、45、52、58）。这些疫苗均基于重组 DNA 技术，由能自我组装形成 HPV 特定空壳（即病毒样颗粒）的纯化 L1 蛋白制成。这些疫苗具有高度免疫原性，并能诱导特异性抗体。治疗性疫苗与预防性疫苗不同，因为它们旨在产生针对转化细胞的细胞介导免疫，而不是中和抗体。在 HPV 蛋白中，E6 和 E7 癌蛋白被认为是宫颈癌免疫治疗的理想靶点，因为它们是恶性肿瘤发生和发展所必需的，并且在癌前病变和侵袭性病变中均持续表达。已经研究了几种用于 HPV 治疗性疫苗的策略，旨在增强 CD4 和 CD8 T 细胞反应，包括基因疫苗（即 DNA/RNA/病毒/细菌）、基于蛋白、肽或树突状细胞的疫苗。然而，目前尚无疫苗获准用于治疗。一些研究表明，在 CIN2 宫颈病变的手术治疗后立即给予预防性疫苗可被视为预防再激活或再感染的辅助手段，其他研究还描述了预防性疫苗在生殖器疣管理中的相关性。本综述总结了主要针对早期癌蛋白 E6 和 E7 的治疗性疫苗和基于 L1 衣壳蛋白的预防性疫苗的主要特征。通过分析这两种疫苗的特异性免疫原性特征，我们讨论了预防性疫苗为何以及如何能有效治疗 HPV 相关病变和复发。
