Protective immunity to rabbit oral and cutaneous papillomaviruses by immunization with short peptides of L2, the minor capsid protein
Protective immunity to rabbit oral and cutaneous papillomaviruses by immunization with short peptides of L2, the minor capsid protein
复制标题
DOI：
10.1128/jvi.76.19.9798-9805.2002
复制
发表时间：
2002-10-01
影响因子：
5.4
通讯作者：
Christensen, ND
中科院分区：
文献类型：
--
作者：
Embers, ME;Budgeon, LR;Christensen, ND
乳头瘤病毒小衣壳蛋白L2已被证明具有免疫原性，由此推断出各种B细胞表位，主要位于L2的氨基末端。然而，在体内对L2的免疫力还没有得到广泛的研究。值得注意的是，人类乳头瘤病毒(HPV)6和16型的共同中和表位被映射到氨基酸(AA)108到120。本研究的目的是利用兔病毒的相应序列从兔身上获得抗血清，并评估这些多肽对感染的保护能力。用兔口腔乳头状瘤病毒(ROPV)和棉尾兔乳头瘤病毒(CRPV)的AA94~122区两个重叠序列的合成肽免疫兔。然后，兔子同时感染ROPV和CRPV，并分别监测口腔和皮肤乳头状瘤的发展情况。用这两种多肽免疫的兔血清显示：(1)与同源病毒纯化的L2发生反应；(2)在病毒感染细胞内特异性识别L2；(3)在体外中和病毒。病毒攻击后，用CRPV多肽免疫的兔皮肤乳头状瘤生长完全消失。同样，ROPV多肽免疫的兔可预防口腔乳头状瘤病。CRPV多肽免疫兔对病毒基因组的攻击导致有效的乳头状瘤生长，提示了一种中和抗体介导的保护机制。这些结果为L2不同区域提供的免疫原性提供了体内证据，并进一步支持了先前关于该区域能够诱导抗病毒免疫的证据。
The papillomavirus minor capsid protein, L2, has been shown to exhibit immunogenicity, whereby a variety of B-cell epitopes, predominantly in the amino terminus of L2, have been deduced. However, immunity to L2 in vivo has not been examined extensively. Notably, a common neutralization epitope for human papillomavirus (HPV) types 6 and 16 was mapped to amino acids (aa) 108 to 120. The objectives of this study were to derive antisera from rabbits using the corresponding sequences from rabbit viruses and to assess the ability of these peptides to protect against infection. Synthetic peptides consisting of two overlapping sequences each in the region of aa 94 to 122 of the rabbit oral (ROPV) and cottontail rabbit (CRPV) papillomaviruses were used to immunize rabbits. Rabbits were then infected with both ROPV and CRPV and monitored for the development of oral and cutaneous papillomas, respectively. Serum derived from rabbits immunized with either of the two peptides was shown to (i) react to purified L2 from the cognate virus, (ii) specifically recognize L2 within virus-infected cells, and (iii) neutralize virus in vitro. Following viral challenge, cutaneous papilloma growth was completely absent in rabbits immunized with either CRPV peptide. Likewise, ROPV peptide-immunized rabbits were protected from oral papillomatosis. Challenge of CRPV peptide-immune rabbits with the viral genome resulted in efficient papilloma growth, suggesting a neutralizing antibody-mediated mechanism of protection. These results afford in vivo evidence for the immunogenicity provided by a distinct region of L2 and further support previous evidence for the ability of this region to elicit antiviral immunity.