Abstract
Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) strategies with proven in vivo efficacy rely on antiretroviral drugs, creating the potential for drug resistance and complicated treatment options in individuals who become infected. Moreover, on-demand products are currently missing from the PrEP development portfolio. Griffithsin (GRFT) is a non-antiretroviral HIV entry inhibitor derived from red algae with an excellent safety profile and potent activity in vitro. When combined with carrageenan (CG), GRFT has strong activity against herpes simplex virus-2 (HSV-2) and human papillomavirus (HPV) in vitro and in vivo. Here, we report that GRFT/CG in a freeze-dried fast dissolving insert (FDI) formulation for on-demand use protects rhesus macaques from a high dose vaginal SHIV SF162P3 challenge 4 h after FDI insertion. Furthermore, the GRFT/CG FDI also protects mice vaginally against HSV-2 and HPV pseudovirus. As a safe, potent, broad-spectrum, on-demand non-antiretroviral product, the GRFT/CG FDI warrants clinical development.
Highlights
Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) strategies with proven in vivo efficacy rely on antiretroviral drugs, creating the potential for drug resistance and complicated treatment options in individuals who become infected
We show that the formulation protects against herpes simplex virus-2 (HSV-2) and human papillomavirus (HPV) infections in mice and provide toxicological and immunological data on repeated dosing that confirm the safety of GRFT/CG
Repeated dosing of GRFT and GRFT/CG in small animal models revealed no adverse findings at any dose levels tested, and showed that GRFT/CG gel is non-irritating (Table 3). 7 days of daily vaginal application of 0.1% GRFT/CG gel did not enhance the susceptibility of mice to HSV-2 infection when compared to the D-PBS control (p = 0.7152, Fisher’s exact test). 14 days of daily intravenous administration of GRFT up to 8.3 mg/kg/day in rats resulted in no detectable anti-drug-antibodies (ADA) and a no adverse effect level (NOAEL) of 8.3 mg/kg/day despite high systemic levels of GRFT
Summary
Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) strategies with proven in vivo efficacy rely on antiretroviral drugs, creating the potential for drug resistance and complicated treatment options in individuals who become infected. Griffithsin (GRFT) is a non-antiretroviral HIV entry inhibitor derived from red algae with an excellent safety profile and potent activity in vitro. Griffithsin (GRFT) is a mannose binding lectin derived from red algae that has an excellent safety profile[5,6,7]. It is the most potent anti-HIV lectin identified to date and among the most potent antiHIV agents[8,9]. CG is already included in many foods and personal care products[2] and is generally recognized as safe (GRAS), which simplifies the regulatory pathway for GRFT/CG products
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
