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; Thomas M. Zydowsky

doi:10.1038/s41467-018-06349-0

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 journal › Article › peer-review

56 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 language	English (US)
Article number	3881
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-06349-0
State	Published - Dec 1 2018
Externally published	Yes

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-018-06349-0

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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, J. D., Peet, M. M., Lloyd, Z., Benson, M., Heneine, W., O’Keefe, B. R., Robbiani, M., ... Zydowsky, T. M. (2018). Griffithsin carrageenan fast dissolving inserts prevent SHIV HSV-2 and HPV infections in vivo. Nature communications, 9(1), Article 3881. https://doi.org/10.1038/s41467-018-06349-0

@article{dda48cc67ce54d5a8c70ea663be44274,

title = "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.",

author = "Nina Derby and Manjari Lal and Meropi Aravantinou and Larisa Kizima and Patrick Barnable and Aixa Rodriguez and Manshun Lai and Asa Wesenberg and Shweta Ugaonkar and Keith Levendosky and Olga Mizenina and Kyle Kleinbeck and Lifson, {Jeffrey D.} and Peet, {M. Melissa} and Zachary Lloyd and Michael Benson and Walid Heneine and O{\textquoteright}Keefe, {Barry R.} and Melissa Robbiani and Elena Martinelli and Brooke Grasperge and James Blanchard and Agegnehu Gettie and Natalia Teleshova and Fern{\'a}ndez-Romero, {Jos{\'e} A.} and Zydowsky, {Thomas M.}",

note = "Funding Information: We thank the veterinary staff at the TNPRC and the CBC at RU for continued support and Randy Fast, Kelli Oswald and Rebecca Shoemaker of the Quantitative Molecular Diagnostics Core of the AIDS and Cancer Virus Program of the Frederick National Laboratory for Cancer Research for expert assistance with plasma viral load measurements. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. The findings and conclusions in this report are ours and do not necessarily represent the views of the Centers for Disease Control and Prevention. This research has been supported by the President{\textquoteright}s Emergency Plan for AIDS Relief (PEPFAR) through the U.S. Agency for International Development (USAID) under the terms of GPO-A-00-04-00019-00, and in part with funds from the National Cancer Institute, NIH, under contract HHSN261200800001E. This study was supported in part by the TNPRC Base Grant P51OD011104-56. Publisher Copyright: {\textcopyright} 2018, The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41467-018-06349-0",

language = "English (US)",

volume = "9",

journal = "Nature communications",

issn = "2041-1723",

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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, Grasperge, B, Blanchard, J, Gettie, A, Teleshova, N, Fernández-Romero, JA & Zydowsky, TM 2018, 'Griffithsin carrageenan fast dissolving inserts prevent SHIV HSV-2 and HPV infections in vivo', Nature communications, vol. 9, no. 1, 3881. https://doi.org/10.1038/s41467-018-06349-0

TY - JOUR

T1 - Griffithsin carrageenan fast dissolving inserts prevent SHIV HSV-2 and HPV infections in vivo

AU - Derby, Nina

AU - Lal, Manjari

AU - Aravantinou, Meropi

AU - Kizima, Larisa

AU - Barnable, Patrick

AU - Rodriguez, Aixa

AU - Lai, Manshun

AU - Wesenberg, Asa

AU - Ugaonkar, Shweta

AU - Levendosky, Keith

AU - Mizenina, Olga

AU - Kleinbeck, Kyle

AU - Lifson, Jeffrey D.

AU - Peet, M. Melissa

AU - Lloyd, Zachary

AU - Benson, Michael

AU - Heneine, Walid

AU - O’Keefe, Barry R.

AU - Robbiani, Melissa

AU - Martinelli, Elena

AU - Grasperge, Brooke

AU - Blanchard, James

AU - Gettie, Agegnehu

AU - Teleshova, Natalia

AU - Fernández-Romero, José A.

AU - Zydowsky, Thomas M.

N1 - Funding Information: We thank the veterinary staff at the TNPRC and the CBC at RU for continued support and Randy Fast, Kelli Oswald and Rebecca Shoemaker of the Quantitative Molecular Diagnostics Core of the AIDS and Cancer Virus Program of the Frederick National Laboratory for Cancer Research for expert assistance with plasma viral load measurements. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. The findings and conclusions in this report are ours and do not necessarily represent the views of the Centers for Disease Control and Prevention. This research has been supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the U.S. Agency for International Development (USAID) under the terms of GPO-A-00-04-00019-00, and in part with funds from the National Cancer Institute, NIH, under contract HHSN261200800001E. This study was supported in part by the TNPRC Base Grant P51OD011104-56. Publisher Copyright: © 2018, The Author(s).

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

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SN - 2041-1723

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ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

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