Leachman S A, Tigelaar R E, Shlyankevich M, Slade M D, Irwin M, Chang E, Wu T C, Xiao W, Pazhani S, Zelterman D, Brandsma J L
Department of Dermatology, School of Medicine, Yale University, New Haven, Connecticut 06520, USA.
J Virol. 2000 Sep;74(18):8700-8. doi: 10.1128/jvi.74.18.8700-8708.2000.
A cottontail rabbit papillomavirus (CRPV) E6 DNA vaccine that induces significant protection against CRPV challenge was used in a superior vaccination regimen in which the cutaneous sites of vaccination were primed with an expression vector encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that induces differentiation and local recruitment of professional antigen-presenting cells. This treatment induced a massive influx of major histocompatibility complex class II-positive cells. In a vaccination-challenge experiment, rabbit groups were treated by E6 DNA vaccination, GM-CSF DNA inoculation, or a combination of both treatments. After two immunizations, rabbits were challenged with CRPV at low, moderate, and high stringencies and monitored for papilloma formation. As expected, all clinical outcomes were monotonically related to the stringency of the viral challenge. The results demonstrate that GM-CSF priming greatly augmented the effects of CRPV E6 vaccination. First, challenge sites in control rabbits (at the moderate challenge stringency) had a 0% probability of remaining disease free, versus a 50% probability in E6-vaccinated rabbits, and whereas GM-CSF alone had no effect, the interaction between GM-CSF priming and E6 vaccination increased disease-free survival to 67%. Second, the incubation period before papilloma onset was lengthened by E6 DNA vaccination alone or to some extent by GM-CSF DNA inoculation alone, and the combination of treatments induced additive effects. Third, the rate of papilloma growth was reduced by E6 vaccination and, to a lesser extent, by GM-CSF treatment. In addition, the interaction between the E6 and GM-CSF treatments was synergistic and yielded more than a 99% reduction in papilloma volume. Finally, regression occurred among the papillomas that formed in rabbits treated with the E6 vaccine and/or with GM-CSF, with the highest regression frequency occurring in rabbits that received the combination treatment.
一种能诱导对棉尾兔乳头瘤病毒（CRPV）攻击产生显著保护作用的CRPV E6 DNA疫苗，被用于一种优化的疫苗接种方案中。在该方案中，用编码粒细胞巨噬细胞集落刺激因子（GM-CSF，一种可诱导专业抗原呈递细胞分化和局部募集的细胞因子）的表达载体对皮肤接种部位进行预处理。这种处理诱导了大量主要组织相容性复合体II类阳性细胞的涌入。在一项疫苗接种-攻击实验中，兔群分别接受E6 DNA疫苗接种、GM-CSF DNA接种或两种处理的组合。两次免疫后，用低、中、高严格度的CRPV对兔子进行攻击，并监测乳头瘤的形成。正如预期的那样，所有临床结果都与病毒攻击的严格度呈单调相关。结果表明，GM-CSF预处理极大地增强了CRPV E6疫苗接种的效果。首先，对照兔（在中等攻击严格度下）的攻击部位无病留存概率为0%，而E6疫苗接种兔为50%，单独使用GM-CSF没有效果，但GM-CSF预处理与E6疫苗接种之间的相互作用使无病生存率提高到了67%。其次，单独的E6 DNA疫苗接种或在一定程度上单独的GM-CSF DNA接种都延长了乳头瘤发病前的潜伏期，两种处理的组合产生了累加效应。第三，E6疫苗接种降低了乳头瘤的生长速度，GM-CSF处理在较小程度上也有此作用。此外，E6和GM-CSF处理之间的相互作用是协同的，使乳头瘤体积减少了99%以上。最后，在用E6疫苗和/或GM-CSF处理的兔子中形成的乳头瘤出现了消退，接受联合处理的兔子消退频率最高。
