Griffithsin carrageenan fast dissolving inserts prevent SHIV HSV-2 and HPV infections in vivo.

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Derby N,Lal M,Aravantinou M,Kizima L,Barnable P,Rodriguez A,Lai M,Wesenberg A,Ugaonkar S,Levendosky K,Mizenina O,Kleinbeck K,Lifson JD,Peet MM,Lloyd Z,Benson M,Heneine W,O'Keefe BR,Robbiani M,Martinelli E,Grasperg

doi

10.1038/s41467-018-06349-0

subject

Has Abstract

pub_date

2018-09-24 00:00:00

pages

3881

issue

1

issn

2041-1723

pii

10.1038/s41467-018-06349-0

journal_volume

9

pub_type

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