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 Martinelli, Brooke Grasperge, James Blanchard, Agegnehu Gettie, Natalia Teleshova, José A. Fernández-Romero and Thomas M. Zydowsky
Additional contact information
Nina Derby: Center for Biomedical Research, Population Council
Manjari Lal: PATH
Meropi Aravantinou: Center for Biomedical Research, Population Council
Larisa Kizima: Center for Biomedical Research, Population Council
Patrick Barnable: Center for Biomedical Research, Population Council
Aixa Rodriguez: Center for Biomedical Research, Population Council
Manshun Lai: PATH
Asa Wesenberg: Center for Biomedical Research, Population Council
Shweta Ugaonkar: Center for Biomedical Research, Population Council
Keith Levendosky: Center for Biomedical Research, Population Council
Olga Mizenina: Center for Biomedical Research, Population Council
Kyle Kleinbeck: Center for Biomedical Research, Population Council
Jeffrey D. Lifson: Frederick National Laboratory for Cancer Research
M. Melissa Peet: MPI Research
Zachary Lloyd: MPI Research
Michael Benson: MPI Research
Walid Heneine: Centers for Disease Control
Barry R O’Keefe: National Cancer Institute
Melissa Robbiani: MJR4CONSULTING
Elena Martinelli: Center for Biomedical Research, Population Council
Brooke Grasperge: Tulane National Primate Research Center
James Blanchard: Tulane National Primate Research Center
Agegnehu Gettie: Aaron Diamond AIDS Research Center
Natalia Teleshova: Center for Biomedical Research, Population Council
José A. Fernández-Romero: Center for Biomedical Research, Population Council
Thomas M. Zydowsky: Center for Biomedical Research, Population Council

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06349-0

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