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

Antiviral Res. 2014 Aug;108:88-93. doi: 10.1016/j.antiviral.2014.05.018. Epub 2014 Jun 5.

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 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.

Keywords: HPV; Microbicides; STI.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravaginal
  • Animals
  • Carrageenan / pharmacology*
  • Carrageenan / therapeutic use*
  • Chemoprevention / methods*
  • Disease Models, Animal
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Inhibitory Concentration 50
  • Luciferases / analysis
  • Luciferases / genetics
  • Mice
  • Microbial Sensitivity Tests
  • Papillomaviridae / drug effects*
  • Papillomavirus Infections / prevention & control*
  • Post-Exposure Prophylaxis / methods
  • Pre-Exposure Prophylaxis / methods
  • Semen / metabolism
  • Treatment Outcome

Substances

  • Carrageenan
  • Luciferases