人乳頭瘤病毒(HPV)感染是美國(guó)最常見(jiàn)的性傳播疾病,常見(jiàn)的癥狀包括生殖器濕疣及肛門生殖器生長(zhǎng),。如果不加治療,,小部分會(huì)引發(fā)腫瘤,。之前的研究顯示,,全世界的子宮頸癌患者中,99.7%感染有HPV,,表明這種病毒會(huì)引發(fā)腫瘤,且預(yù)防性HPV接種可以預(yù)防這種疾病,。在15種會(huì)引發(fā)腫瘤的HPV類別中,,HPV16最為常見(jiàn),然后是HPV18和HPV45(它們引發(fā)的子宮頸癌病例分別占全球子宮頸癌病例的50%,、20%和10%),。
Hannah Alphs所領(lǐng)導(dǎo)的研究小組給小鼠接種了取自HPV16的一小部分蛋白,然后測(cè)試這是否可以保護(hù)小鼠免受HPV16及其它誘癌病株的感染,。研究人員發(fā)現(xiàn),,給小鼠的皮下注射或者鼻噴射修飾后的HPV16蛋白后,小鼠不僅能對(duì)HPV16免疫,,對(duì)HPV45也有免疫表現(xiàn),。研究人員表示,這種疫苗不同于當(dāng)前用于患者的HPV治療法,,它無(wú)需針頭也可接種,,而且免疫范圍很廣,對(duì)多種HPV毒株均有效,。相關(guān)論文發(fā)表在美國(guó)《國(guó)家科學(xué)院院刊》上,。(來(lái)源:Eurekalert!中文版)
生物谷推薦原始出處:
(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.