Gupta Chamma, Dolma Karma G, Sherpa Mingma L, Bag Arundhati, Byahut Abhishek
Department of Biochemistry, Sikkim Manipal Institute of Medical Sciences, Sikkim Manipal University, Gangtok 737102, Sikkim, India.
J Biosci. 2025;50.
Persistent infection with high-risk human papillomavirus (HPV) is a major etiological cause of cancers associated with the cervix, anogenital region, vulva, vagina, penis, and oropharynx. Cervarix®, Gardasil®, and Gardsil9® are three approved prophylactic vaccines that can effectively provide protection against HPV infection. However,they only offer protection against a limited number of HPV strains, not all of which can cause cervical cancer (CC). Additionally, they only provide limited therapeutic advantages against HPV infections that have already been established. Thus, developing a therapeutic vaccine is urgently required and is the need of the hour. Unlike normal cells, two of the viral early proteins, E6 and E7, are persistently expressed in tumor cells. This makes these two proteins the prime candidates for therapeutic vaccines that aim to eliminate the infected cells by cytotoxic T-lymphocytes without affecting normal cells. Therapeutic vaccinations are being researched and are under trials, and no such vaccines have yet been authorized. The development of a therapeutic vaccination coupled with currently available prophylactic vaccines is anticipated to significantly lower morbidity and cancer load globally. This review aims to provide a clear understanding of the molecular basis, immunogenicity, effectiveness, and challenges of current prophylactic vaccines and the future scope of implementing therapeutic vaccines against infection caused by HPV.
高危型人乳头瘤病毒（HPV）的持续感染是导致子宫颈、肛门生殖器区域、外阴、阴道、阴茎和口咽相关癌症的主要病因。希瑞适（Cervarix®）、佳达修（Gardasil®）和九价重组人乳头瘤病毒疫苗（Gardsil9®）是三种已获批准的预防性疫苗，可有效预防HPV感染。然而，它们仅能预防有限数量的HPV毒株，并非所有这些毒株都会引发宫颈癌（CC）。此外，对于已经发生的HPV感染，它们的治疗优势也较为有限。因此，迫切需要研发一种治疗性疫苗，这是当务之急。与正常细胞不同，病毒的两种早期蛋白E6和E7在肿瘤细胞中持续表达。这使得这两种蛋白成为治疗性疫苗的主要候选对象，这类疫苗旨在通过细胞毒性T淋巴细胞消除感染细胞，同时不影响正常细胞。治疗性疫苗正在研究和试验中，尚未有此类疫苗获得批准。预计将治疗性疫苗与现有的预防性疫苗相结合，可显著降低全球的发病率和癌症负担。本综述旨在清晰阐述当前预防性疫苗的分子基础、免疫原性、有效性和挑战，以及实施针对HPV感染的治疗性疫苗的未来前景。
