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

Nina Derby*, Manjari Lal, Meropi Aravantinou, Larisa Kizima, Patrick Barnable, Aixa Rodriguez, Manshun Lai, Asa Wesenberg, Shweta Ugaonkar, Keith Levendosky, Olga Mizenina, Kyle Kleinbeck, Jeffrey D. Lifson, M. Melissa Peet, Zachary Lloyd, Michael Benson, Walid Heneine, Barry R. O’Keefe, Melissa Robbiani, Elena MartinelliBrooke Grasperge, James Blanchard, Agegnehu Gettie, Natalia Teleshova, José A. Fernández-Romero, Thomas M. Zydowsky

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Article number3881
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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