In vivo mechanisms of vaccine-induced protection against HPV infection.

In vivo mechanisms of vaccine-induced protection against HPV infection.
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DOI:
10.1016/j.chom.2010.08.003
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发表时间:
2010-09-16
影响因子:
30.3
通讯作者:
Schiller JT
Schiller JT
中科院分区:
医学1区
文献类型:
--
作者:
Day PM;Kines RC;Thompson CD;Jagu S;Roden RB;Lowy DR;Schiller JT

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使用人乳头瘤病毒(HPV)宫颈阴道小鼠攻击模型,我们在显微镜下研究了L1病毒样颗粒(VLP)和L2疫苗诱导的感染抑制的体内机制。体内HPV感染需要与脱细胞基底膜(BM)的初始缔合以诱导病毒体的构象变化,从而允许其与角质形成细胞表面缔合。通过被动转移免疫血清,我们确定抗L1抗体可以在两个阶段干扰感染。类似于主动VLP免疫,高L1抗体浓度的转移阻止BM结合。在存在低浓度的抗L1抗体时,未检测到与BM相关的病毒体与上皮细胞表面的结合。无论浓度如何,L2疫苗诱导的抗体允许BM缔合,但阻止与细胞表面缔合。这是第一个研究疫苗诱导的体内抑制病毒感染的机制。
Using a human papillomavirus (HPV) cervicovaginal murine challenge model, we microscopically examined the in vivo mechanisms of L1 virus-like particle (VLP) and L2 vaccine-induced inhibition of infection. In vivo HPV infection requires an initial association with the acellular basement membrane (BM) to induce conformational changes in the virion that permit its association with the keratinocyte cell surface. By passive transfer of immune serum, we determined that anti-L1 antibodies can interfere with infection at two stages. Similarly to active VLP immunization, transfer of high L1 antibody concentrations prevented BM binding. In the presence of low concentrations of anti-L1 antibodies, virions associated with the BM, however binding to the epithelial cell surface was not detected. Regardless of the concentration, L2 vaccine-induced antibodies allow BM association, but prevent association with the cell surface. This is the first study to examine the mechanisms of vaccine-induced inhibition of virus infection in vivo.
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