Rodríguez Aixa, Kleinbeck Kyle, Mizenina Olga, Kizima Larisa, Levendosky Keith, Jean-Pierre Ninochka, Villegas Guillermo, Ford Brian E, Cooney Michael L, Teleshova Natalia, Robbiani Melissa, Herold Betsy C, Zydowsky Thomas, Fernández Romero José A
The Population Council, New York, NY, USA.
Albert Einstein College of Medicine, Bronx, NY, USA.
Antiviral Res. 2014 Aug;108:88-93. doi: 10.1016/j.antiviral.2014.05.018. Epub 2014 Jun 5.
Commercial vaccines against human papillomavirus (HPV) have low uptake due to parental autonomy, dosing regimen, cost, and cold chain storage requirements. Carrageenan (CG)-based formulations prevent HPV infection in vitro and in vivo but data are needed on the durability of anti-HPV activity and the effect of seminal plasma (SP). The Population Council's PC-515 gel and the lubricant Divine 9 were tested for their physicochemical properties and anti-HPV activity against HPV16, 18, and 45 pseudoviruses (PsVs). Anti-PsV activity was estimated using the luciferase assay in HeLa cells and the HPV PsV luciferase mouse model. Formulations were applied intravaginally either 2h pre/2h post (-2h/+2h) or 24h pre (-24h) relative to challenge with HPV16 or 45 PsV in PBS or SP/PBS. Both formulations showed broad-spectrum anti-HPV activity in vitro (IC50: 1-20ng/ml), significantly decreasing HPV PsV infection in the mouse model (-2h/+2h, p<0.0001). PC-515 protected better than Divine 9 in the -24h dosing regimen (p<0.0001) and comparable to Divine 9 in the -2h/+2h regimen (p=0.9841). PC-515 retained full activity in the murine model when PsV solutions contained human SP. The durable, potential broad-spectrum anti-HPV activity of CG formulations in the presence of SP supports their further development to prevent HPV acquisition.
针对人乳头瘤病毒（HPV）的商用疫苗接种率较低，原因包括家长自主决定权、给药方案、成本以及冷链储存要求等。基于角叉菜胶（CG）的制剂在体外和体内均能预防HPV感染，但仍需要有关抗HPV活性耐久性和精浆（SP）影响的数据。对人口理事会的PC - 515凝胶和润滑剂Divine 9进行了理化性质测试以及针对HPV16、18和45型假病毒（PsV）的抗HPV活性测试。使用HeLa细胞中的荧光素酶测定法和HPV PsV荧光素酶小鼠模型评估抗PsV活性。相对于在PBS或SP/PBS中用HPV16或45型PsV进行攻击，在攻击前2小时/攻击后2小时（-2小时/+2小时）或攻击前24小时（-24小时）经阴道给予制剂。两种制剂在体外均显示出广谱抗HPV活性（IC50：1 - 至20纳克/毫升），在小鼠模型中显著降低HPV PsV感染（-2小时/+2小时，p<0.0001）。在-24小时给药方案中，PC - 515的保护效果优于Divine 9（p<0.0001），在-2小时/+2小时给药方案中与Divine 9相当（p = 0.9841）。当PsV溶液含有人类SP时，PC - 515在小鼠模型中保持了全部活性。CG制剂在存在SP的情况下具有持久的、潜在的广谱抗HPV活性，这支持它们进一步开发以预防HPV感染。
