Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY, 10065, USA.
PATH, 2201 Westlake Ave, Suite 200, Seattle, WA, 98121, USA.
Nat Commun. 2018 Sep 24;9(1):3881. doi: 10.1038/s41467-018-06349-0.
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.
人类免疫缺陷病毒(HIV)暴露前预防(PrEP)策略依赖于已被证实具有体内疗效的抗逆转录病毒药物,这为感染的个体带来了耐药性和复杂治疗选择的潜在风险。此外,按需产品目前在 PrEP 开发组合中缺失。Griffithsin(GRFT)是一种源自红藻的非抗逆转录病毒 HIV 进入抑制剂,具有出色的安全性和体外强效活性。当与角叉菜胶(CG)联合使用时,GRFT 在体外和体内对单纯疱疹病毒-2(HSV-2)和人乳头瘤病毒(HPV)具有强大的活性。在这里,我们报告说,GRFT/CG 在一种用于按需使用的冻干速溶插入物(FDI)配方中,可在 FDI 插入后 4 小时保护恒河猴免受高剂量阴道 SHIV SF162P3 挑战。此外,GRFT/CG FDI 还可保护小鼠阴道免受 HSV-2 和 HPV 假病毒的侵害。作为一种安全、强效、广谱、按需的非抗逆转录病毒产品,GRFT/CG FDI 值得临床开发。