Intracutaneous vaccination of rabbits with the E6 gene of cottontail rabbit papillomavirus provides partial protection against virus challenge.
Intracutaneous vaccination of rabbits with the E6 gene of cottontail rabbit papillomavirus provides partial protection against virus challenge.
复制标题
用棉尾兔乳头瘤病毒 E6 基因对兔子进行皮内疫苗接种可提供针对病毒攻击的部分保护。
DOI：
10.1016/s0264-410x(97)84510-0
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发表时间：
1998
期刊：
影响因子：
5.5
通讯作者：
Brandsma,JL
中科院分区：
文献类型：
--
作者：
Sundaram,P;Tigelaar,RE;Xiao,W;Brandsma,JL
用棉尾兔乳头瘤病毒(CRPV)的L1基因DNA免疫兔皮肤，已被证明能诱导针对CRPV的预防性免疫。我们现在使用相同的方法描述接种CRPVE6基因的效果。实验疫苗pdCMV-E6编码CRPVE6蛋白的截短和全长两种形式。对照疫苗pCMV-β编码β半乳糖苷酶。用基因枪给兔子接种包被DNA的金颗粒。每只兔先接种30μg脱氧核糖核酸，3周后加强免疫，同样接种30μg脱氧核糖核酸。PdCMV-E6免疫兔在攻击前通过外周血单核细胞增殖试验检测到E6特异性细胞免疫，但没有产生可检测到的对E6蛋白的体液免疫，通过使用两种不同的E6抗原制备的ELISA法进行评估。对照组兔产生对β半乳糖苷酶的体液免疫。所有兔用活CRPV病毒感染9个皮肤部位，观察乳头状瘤的形成。在任何一个挑战点，四只对照兔都没有受到保护。在接种pdCMV-E6疫苗的六只兔子中，两只完全保护，一只几乎完全保护(九个挑战部位中只有两个出现微小乳头状瘤)。这三只兔在体外也表现出显著的E6特异性增殖反应。未完全保护的四只接种E6 DNA的兔子显示出部分保护的证据：一些挑战部位没有形成乳头状瘤；乳头状瘤发病延迟；乳头状瘤负担较小。这些结果表明，通过皮内接种编码乳头瘤病毒E6蛋白的重组质粒可以部分预防乳头瘤病毒诱导的疾病。
DNA vaccination of rabbit skin with the L1 gene of cottontail rabbit papillomavirus (CRPV) has previously been shown to induce prophylactic immunity against CRPV. We now describe the effects of vaccination with the CRPV E6 gene, using the same approach. The experimental vaccine pdCMV-E6 encoded both the truncated and full length forms of CRPV E6 protein. The control vaccine pCMV-β encoded β galactosidase. Rabbits were vaccinated with DNA-coated gold particles, using a gene gun. Each rabbit received an initial vaccination with 30 μg DNA and 3 weeks later a booster vaccination, also with 30 μg DNA. pdCMV-E6-vaccinated rabbits developed E6-specific cellular immunity as determined by proliferation assays using peripheral blood mononuclear cells from animals prior to challenge, but did not develop detectable humoral immunity to E6 proteins, as evaluated by ELISA using two different E6 antigen preparations. Control rabbits developed humoral immunity to β galactosidase. All rabbits were challenged by infection of nine skin sites with live CRPV virus and monitored for papilloma formation. None of four control rabbits was protected at any of the challenge sites. Of six rabbits vaccinated with pdCMV-E6, two were completely protected and one was virtually completely protected (tiny papillomas at just two of nine challenge sites). These three rabbits also exhibited significant E6-specific in vitro proliferative responses. The four E6 DNA-vaccinated rabbits that were not completely protected exhibited evidence of partial protection: some challenge sites did not form papillomas; papilloma onset was delayed; papilloma burden was less. These results demonstrate that partial prophylaxis against papillomavirus-induced disease can be achieved by intracutaneous vaccination with a recombinant plasmid encoding the papillomavirus E6 protein.