In vitro and in vivo evaluation of two carrageenan-based formulations to prevent HPV acquisition

作者：Rodriguez 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; Romero Jose A Fernandez^*

来源：Antiviral Research, 2014, 108: 88-93.

DOI：10.1016/j.antiviral.2014.05.018

• HPV
• STI
• Microbicides

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 2 h pre/2 h post (-2 h/+2 h) or 24 h pre (-24 h) relative to challenge with HPV16 or 45 PsV in PBS or SP/PBS.
Both formulations showed broad-spectrum anti-HPV activity in vitro (IC50: 1-20 ng/ml), significantly decreasing HPV PsV infection in the mouse model (-2 h/+2 h, p <0.0001). PC-515 protected better than Divine 9 in the 24 h dosing regimen (p < 0.0001) and comparable to Divine 9 in the 2 h/+2 h 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.

• 出版日期2014-8