Moniz Michelle, Ling Morris, Hung Chien-Fu, Wu T-C
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Front Biosci. 2003 Jan 1;8:d55-68. doi: 10.2741/936.
Human papillomaviruses (HPV), particularly HPV type 16, are the primary etiologic agent of cervical cancer. Thus, HPV-associated cervical malignancies might be prevented or treated by induction of the appropriate virus-specific immune responses in patients. HPV capsid proteins including L1 and L2 proteins have been shown to generate neutralizing antibodies against HPV particles in vaccinated individuals. Furthermore, HPV oncogenic proteins such as E6 and E7 proteins are important in the induction and maintenance of cellular transformation and are co-expressed in the majority of HPV-containing carcinomas. They represent ideal targets for the development of therapeutic vaccines against HPV infections and HPV-associated neoplasia. Vaccines targeting these proteins may provide an opportunity to control HPV-associated malignancies. Genetic immunization with naked DNA has emerged as an important strategy for vaccine development. Plasmid DNA encoding antigen of interest, such as capsid protein L1 and L2 (for preventive vaccines) and non-structural proteins E6 and E7 (for therapeutic vaccines) enters the host and stimulates an antigen-specific humoral and cellular immune response. Various strategies to enhance preventive and therapeutic effects of DNA vaccines are currently under active investigation. Should they fulfill their promise, these DNA vaccines may prevent HPV infection or control HPV-related cervical lesions.
人乳头瘤病毒(HPV),尤其是16型HPV,是宫颈癌的主要病因。因此,通过诱导患者产生适当的病毒特异性免疫反应,HPV相关的宫颈恶性肿瘤可能得以预防或治疗。HPV衣壳蛋白,包括L1和L2蛋白,已被证明能在接种疫苗的个体中产生针对HPV颗粒的中和抗体。此外,HPV致癌蛋白,如E6和E7蛋白,在细胞转化的诱导和维持中起重要作用,并且在大多数含HPV的癌组织中共同表达。它们是开发针对HPV感染和HPV相关肿瘤的治疗性疫苗的理想靶点。针对这些蛋白的疫苗可能提供控制HPV相关恶性肿瘤的机会。裸DNA基因免疫已成为疫苗开发的一项重要策略。编码感兴趣抗原的质粒DNA,如衣壳蛋白L1和L2(用于预防性疫苗)以及非结构蛋白E6和E7(用于治疗性疫苗)进入宿主并刺激抗原特异性体液和细胞免疫反应。目前正在积极研究各种增强DNA疫苗预防和治疗效果的策略。如果这些DNA疫苗能实现其预期效果,它们可能预防HPV感染或控制HPV相关的宫颈病变。