Preclinical evaluation of high-dose Griffithsin carrageenan fast-dissolving insert for HIV, HSV-2, and HPV prevention

Document Type

Article (peer-reviewed)

Publication Date

4-20-2026

Abstract

Griffithsin (GRFT) is an antiviral lectin that blocks human immunodeficiency virus (HIV) entry. When combined with carrageenan (CG), GRFT has strong activity against herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV). We conducted a preclinical evaluation of a high-dose vaginal fast-dissolving insert (FDI) containing 3 mg GRFT—equivalent to 3× the clinical dose—and compared it with a 1 mg formulation. Studies included FDI disintegration (macaques, rabbits); GRFT pharmacokinetics, pharmacodynamics, and inflammatory response (macaques); toxicity (rats); and immunogenicity (macaques, rats). Disintegration times varied between species, emphasizing the importance of evaluating this parameter in humans. In macaques, cervico-vaginal lavage (CVL) GRFT concentrations exceeded levels associated with in vivo efficacy 12 h after administration of the 3 mg GRFT/CG FDI. Potent anti-HIV1BaL activity was detected in CVLs collected 24 h following the 3 mg dose and 12 h after the 1 mg dose. CVLs inhibited HSV-2 at 4 h and HPV at 12 h after both GRFT doses. GRFT/CG FDIs caused no inflammatory response and did not alter vaginal pH. In rats, repeated daily dosing at up to 10× the clinical dose revealed no safety concerns. Although anti-drug antibodies (ADAs) developed in macaques and rats, systemic GRFT was undetectable, suggesting that ADAs are unlikely to alter pharmacokinetics. Overall, the CVL GRFT concentrations and anti-HIV activity following administration of 3 mg GRFT/CG FDIs suggest a longer protection window—at least 12 h—against HIV-1 compared with the 1 mg FDI, and both formulations demonstrate activity against HSV-2 and HPV. These findings support continued GRFT/CG FDI development.

DOI

10.1128/spectrum.01966-25

Language

English

https://doi.org/10.1128/spectrum.01966-25

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