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

Aixa Rodríguez, Kyle Kleinbeck, Olga Mizenina, Larisa Kizima, Keith Levendosky, Ninochka Jean-Pierre, Guillermo Villegas, Brian E. Ford, Michael L. Cooney, Natalia Teleshova, Melissa Robbiani, Betsy C. Herold, Thomas Zydowsky, José A. Fernández Romero

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

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 (IC 50: 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.

Original languageEnglish (US)
Pages (from-to)88-93
Number of pages6
JournalAntiviral Research
Volume108
Issue number1
DOIs
StatePublished - Aug 2014

Keywords

  • HPV
  • Microbicides
  • STI

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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    Rodríguez, A., Kleinbeck, K., Mizenina, O., Kizima, L., Levendosky, K., Jean-Pierre, N., Villegas, G., Ford, B. E., Cooney, M. L., Teleshova, N., Robbiani, M., Herold, B. C., Zydowsky, T., & Fernández Romero, J. A. (2014). In vitro and in vivo evaluation of two carrageenan-based formulations to prevent HPV acquisition. Antiviral Research, 108(1), 88-93. https://doi.org/10.1016/j.antiviral.2014.05.018