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

Author

Listed:
  • 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
    Borough of Manhattan Community College)

  • Thomas M. Zydowsky

    (Center for Biomedical Research, Population Council)

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.

Suggested Citation

  • Nina Derby & Manjari Lal & Meropi Aravantinou & Larisa Kizima & Patrick Barnable & Aixa Rodriguez & Manshun Lai & Asa Wesenberg & Shweta Ugaonkar & Keith Levendosky & Olga Mizenina & Kyle Kleinbeck & , 2018. "Griffithsin carrageenan fast dissolving inserts prevent SHIV HSV-2 and HPV infections in vivo," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06349-0
    DOI: 10.1038/s41467-018-06349-0
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