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利用含有L2衣壳表位的重组烟草花叶病毒保护兔子免受皮肤乳头瘤病毒感染。

Protection of rabbits against cutaneous papillomavirus infection using recombinant tobacco mosaic virus containing L2 capsid epitopes.

作者信息

Palmer Kenneth E, Benko Ann, Doucette Sarah A, Cameron Terri I, Foster Tiffany, Hanley Kathleen M, McCormick Alison A, McCulloch Michael, Pogue Gregory P, Smith Mark L, Christensen Neil D

机构信息

Large Scale Biology Corporation, 3333 Vaca Valley Parkway, Vacaville, CA 95688, USA.

出版信息

Vaccine. 2006 Jun 29;24(26):5516-25. doi: 10.1016/j.vaccine.2006.04.058. Epub 2006 May 6.

DOI:10.1016/j.vaccine.2006.04.058
PMID:16725236
Abstract

Cottontail rabbit papillomavirus (CRPV) and rabbit oral papillomavirus (ROPV) represent distantly related, cutaneous and mucosal tissue tropic papillomaviruses respectively that can infect the same host. These two viruses were used to test the effectiveness of an L2 peptide-based vaccine (aa 94-122) that was delivered on the surface of recombinant tobacco mosaic virus (rTMV) particles. Groups of NZW rabbits received combinations of CRPVL2, ROPVL2 and CRPV+ROPVL2 rTMV vaccines, and were then challenged with infectious CRPV and ROPV. The rabbits developed antibodies that reacted to whole L2 protein and these sera were able to neutralize CRPV pseudovirions at half-maximal titers that were between 50 and 500. Rabbits receiving the CRPV L2 vaccine alone or in combination with ROPV L2 vaccines were completely protected against CRPV infections. Those rabbits vaccinated with the ROPV L2 vaccines showed a weak response in some rabbits against CRPV infection. These studies demonstrate that L2-based vaccines provide strong protection against experimental papillomavirus infection that is most likely based upon the induction of virus-neutralizing antibody. Notably, we observed some limited cross-protection induced by the L2 sequences tested in these vaccines. Finally, the study demonstrated that rTMV were excellent agents for the induction of strong protection in a pre-clinical disease model of papillomavirus infection.

摘要

棉尾兔乳头瘤病毒(CRPV)和兔口腔乳头瘤病毒(ROPV)分别代表亲缘关系较远、具有皮肤和粘膜组织嗜性的乳头瘤病毒,它们可感染同一宿主。这两种病毒被用于测试基于L2肽的疫苗(氨基酸94 - 122)的有效性,该疫苗搭载于重组烟草花叶病毒(rTMV)颗粒表面。将新西兰白兔分组,分别接种CRPVL2、ROPVL2和CRPV + ROPVL2 rTMV疫苗组合,随后用感染性CRPV和ROPV进行攻毒。兔子产生了与完整L2蛋白反应的抗体,这些血清能够以50至500之间的半数最大效价中和CRPV假病毒颗粒。单独接种CRPV L2疫苗或与ROPV L2疫苗联合接种的兔子对CRPV感染具有完全的保护作用。接种ROPV L2疫苗的兔子中,部分兔子对CRPV感染表现出较弱的反应。这些研究表明,基于L2的疫苗对实验性乳头瘤病毒感染具有强大的保护作用,这很可能是基于病毒中和抗体的诱导。值得注意的是,我们观察到这些疫苗中测试的L2序列诱导了一些有限的交叉保护作用。最后,该研究表明,rTMV是在乳头瘤病毒感染的临床前疾病模型中诱导强大保护作用的优秀载体。

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