人乳头瘤病毒（HPV）感染是美国最常见的性传播疾病，常见的症状包括生殖器湿疣及肛门生殖器生长。如果不加治疗，小部分会引发肿瘤。之前的研究显示，全世界的子宫颈癌患者中，99.7%感染有HPV，表明这种病毒会引发肿瘤，且预防性HPV接种可以预防这种疾病。在15种会引发肿瘤的HPV类别中，HPV16最为常见，然后是HPV18和HPV45（它们引发的子宫颈癌病例分别占全球子宫颈癌病例的50%、20%和10%）。
Hannah Alphs所领导的研究小组给小鼠接种了取自HPV16的一小部分蛋白，然后测试这是否可以保护小鼠免受HPV16及其它诱癌病株的感染。研究人员发现，给小鼠的皮下注射或者鼻喷射修饰后的HPV16蛋白后，小鼠不仅能对HPV16免疫，对HPV45也有免疫表现。研究人员表示，这种疫苗不同于当前用于患者的HPV治疗法，它无需针头也可接种，而且免疫范围很广，对多种HPV毒株均有效。相关论文发表在美国《国家科学院院刊》上。（来源：Eurekalert！中文版）
生物谷推荐原始出处：
（PNAS），10.1073/pnas.0800868105，Hannah H. Alphs, Richard B. S. Roden
Protection against heterologous human papillomavirus challenge by a synthetic lipopeptide vaccine containing a broadly cross-neutralizing epitope of L2
Hannah H. Alphs*, Ratish Gambhira*,, Balasubramanyam Karanam*, Jeffrey N. Roberts, Subhashini Jagu*, John T. Schiller, Weiguang Zeng,¶, David C. Jackson,¶, and Richard B. S. Roden*,||,**
Departments of *Pathology, ||Oncology, and Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD 21231; National Cancer Institute, Bethesda, MD 20892; Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Victoria, Australia; and ¶VacTX Pty. Ltd., Level 10 (South), 459 Collins Street, Melbourne 3000, Victoria, Australia
Edited by Peter M. Howley, Harvard Medical School, Boston, MA, and approved March 6, 2008 (received for review January 28, 2008)
Abstract
Persistent infection with the high-risk subset of genitotropic human papillomavirus (HPV) genotypes is a necessary cause of cervical cancer. Given the global burden of cervical cancer, a low-cost, broadly protective vaccine is needed. RG-1 is a cross-neutralizing and protective monoclonal antibody that recognizes residues 17–36 of HPV16 minor capsid protein L2. Because this epitope is highly conserved in divergent HPV types, we determined whether vaccination with HPV16 L2 17–36 peptide is broadly protective. The peptide was administered to BALB/c mice three times at monthly intervals, either alone or in the context of a synthetic lipopeptide vaccine candidate (P25-P2C-HPV) produced by linkage of the HPV peptide with a broadly recognized T helper epitope (P25) and the Toll-like receptor-2 (TLR2) ligand dipalmitoyl-S-glyceryl cysteine (P2C). In contrast to vaccination with the L2 17–36 peptide or P25-P2C alone, a potent L2-specific antibody response was generated to the P25-P2C-HPV lipopeptide when delivered either s.c. or intranasally. Sera from mice vaccinated with the P25-P2C-HPV lipopeptide neutralized not only HPV16 pseudovirions but also other evolutionarily divergent oncogenic genital (HPV18, HPV45) and cutaneous (HPV5, BPV1) types. The L2-specific antibody response depended on MHC class II, CD40, and MyD88 signaling. Additionally, vaccination with the P25-P2C-HPV lipopeptide protected mice from homologous challenge with HPV16 pseudovirions at cutaneous and genital sites and heterologous challenge with HPV45 pseudovirions. If provided in the appropriate context, therefore, HPV16 L2 17–36 might be used in a totally synthetic cross-protective HPV vaccine.
