Background Human papillomavirus (HPV) constitutes one of the major sexually transmitted viral infections. Vaccines against HPV are commercially available but vaccination rates are currently low around the world due to parental autonomy, three dose regimen, cost and the need for cold chain storage. In vitro and in vivo data have indicated that carrageenan (CG)-based microbicide formulations may prevent HPV infection but additional data is needed to assess the durability of this antiviral activity and the effect of biological fluids.

Methods A proprietary 3% CG gel formulation (Population Council) and the commercial sexual lubricant Divine 9 were tested for their anti-HPV activity against HPV16, 18, and 45 pseudoviruses (PsVs). The anti-HPV PsV activity was estimated using the in vitro luciferase assay in HeLa cells and IC₅₀ values were calculated using a dose-response-inhibition analysis on GraphPad Prism v5.0 software. The HPV PsV luciferase mouse model was performed to test the in vivo activity of the gels. The formulations were applied intravaginally in a BAT24 (–2h/+2h) dosing regimen or in a single –24h application before challenging with HPV16 or 45 PsV in PBS or seminal plasma. In vivo luciferase expression was measured 24h later and the Mann Whitney U test (P < 0.05) was used for statistical analyses.

Results Both CG and Divine 9 showed broad-spectrum anti-HPV activity in vitro (IC₅₀: 1–20ng/ml) and significantly decreased HPV PsV infection in the mouse model; the in-house formulation afforded better protection than Divine 9 in the BAT24 (p = 0.0101) or the single –24h application (p = 0.0008) dosing regimens. CG formulations retained full activity in the murine model when PsVs were mixed with human seminal plasma.

Conclusions The potential broad-spectrum activity of CG formulations and the durability of protection, even in the presence of seminal plasma, supports further advancement of CG to prevent HPV acquisition.