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

被引：69

作者：

Derby, Nina ^{[1
]}

Lal, Manjari ^{[2
]}

Aravantinou, Meropi ^{[1
]}

Kizima, Larisa ^{[1
]}

Barnable, Patrick ^{[1
]}

Rodriguez, Aixa ^{[1
]}

Lai, Manshun ^{[2
]}

Wesenberg, Asa ^{[1
]}

Ugaonkar, Shweta ^{[1
]}

Levendosky, Keith ^{[1
]}

Mizenina, Olga ^{[1
]}

Kleinbeck, Kyle ^{[1
]}

Lifson, Jeffrey D. ^{[3
]}

Peet, M. Melissa ^{[4
]}

Lloyd, Zachary ^{[4
]}

Benson, Michael ^{[4
]}

Heneine, Walid ^{[5
]}

O'Keefe, Barry R. ^{[6
,7
]}

Robbiani, Melissa ^{[8
]}

Martinelli, Elena ^{[1
]}

Grasperge, Brooke ^{[9
]}

Blanchard, James ^{[9
]}

Gettie, Agegnehu ^{[10
]}

Teleshova, Natalia ^{[1
]}

Fernandez-Romero, Jose A. ^{[1
,11
]}

Zydowsky, Thomas M. ^{[1
]}

机构：

[1] Populat Council, Ctr Biomed Res, 1230 York Ave, New York, NY 10065 USA

[2] PATH, 2201 Westlake Ave,Suite 200, Seattle, WA 98121 USA

[3] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, 8560 Progress Dr, Frederick, MD 21701 USA

[4] MPI Res, 54943 N Main St, Mattawan, MI 49071 USA

[5] Ctr Dis Control, 1600 Clifton Rd, Atlanta, GA 30333 USA

[6] NCI, Ctr Canc Res, Mol Targets Program, Bldg 560,Room 21-105, Frederick, MD 21702 USA

[7] NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Bldg 560,Room 21-105, Frederick, MD 21702 USA

[8] MJR4CONSULTING, New York, NY 10065 USA

[9] Tulane Natl Primate Res Ctr, 18703 Three Rivers Rd, Covington, LA 70433 USA

[10] Aaron Diamond AIDS Res Ctr, 455 1st Ave 7, New York, NY 10016 USA

[11] Borough Manhattan Community Coll, Sci Dept, 199 Chambers St, New York, NY 10007 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

HERPES-SIMPLEX-VIRUS; HUMAN-PAPILLOMAVIRUS; CYANOVIRIN-N; PREEXPOSURE PROPHYLAXIS; VAGINAL TRANSMISSION; INTRAVAGINAL RINGS; RHESUS MACAQUES; AFRICAN WOMEN; HIV-INFECTION; RT INFECTION;

D O I：

10.1038/s41467-018-06349-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：9

共 60 条

[11] Carrageenan is a potent inhibitor of papillomavirus infection [J].

Buck, Christopher B. ;

Thompson, Cynthia D. ;

Roberts, Jeffrey N. ;

Mueller, Martin ;

Lowy, Douglas R. ;

Schiller, John T. .

PLOS PATHOGENS, 2006, 2 (07) :671-680

[12] ANALYSIS OF PUTATIVE MUCOSAL SHIV SUSCEPTIBILITY FACTORS DURING REPEATED DMPA TREATMENTS IN PIGTAIL MACAQUES [J].

Butler, Katherine ;

Ritter, Jana ;

Ellis, Shanon ;

Henning, Tara ;

Montague, Jeltley ;

Zaki, Sherif ;

Garber, David ;

McNicholl, Janet ;

Kersh, Ellen .

JOURNAL OF MEDICAL PRIMATOLOGY, 2015, 44 (05) :325-325

[13] MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa [J].

Calenda, Giulia ;

Villegas, Guillermo ;

Barnable, Patrick ;

Litterst, Claudia ;

Levendosky, Keith ;

Gettie, Agegnehu ;

Cooney, Michael L. ;

Blanchard, James ;

Fernandez-Romero, Jose A. ;

Zydowsky, Thomas M. ;

Teleshova, Natalia .

JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2017, 74 (03) :E67-E74

[14] Viral burden in genital secretions determines male-to-female sexual transmission of HIV-1: a probabilistic empiric model [J].

Chakraborty, H ;

Sen, PK ;

Helms, RW ;

Vernazza, PL ;

Fiscus, SA ;

Eron, JJ ;

Patterson, BK ;

Coombs, RW ;

Krieger, JN ;

Cohen, MS .

AIDS, 2001, 15 (05) :621-627

[15]

Davis D., 2011, NCBI GENPEPT

[16] An intravaginal ring that releases three antiviral agents and a contraceptive blocks SHIV-RT infection, reduces HSV-2 shedding, and suppresses hormonal cycling in rhesus macaques [J].

Derby, Nina ;

Aravantinou, Meropi ;

Kenney, Jessica ;

Ugaonkar, Shweta R. ;

Wesenberg, Asa ;

Wilk, Jolanta ;

Kizima, Larisa ;

Rodriguez, Aixa ;

Zhang, Shimin ;

Mizenina, Olga ;

Levendosky, Keith ;

Cooney, Michael L. ;

Seidor, Samantha ;

Gettie, Agegnehu ;

Grasperge, Brooke ;

Blanchard, James ;

Piatak, Michael, Jr. ;

Lifson, Jeffrey D. ;

Fernandez-Romero, Jose ;

Zydowsky, Thomas M. ;

Robbiani, Melissa .

DRUG DELIVERY AND TRANSLATIONAL RESEARCH, 2017, 7 (06) :840-858

[17]

Fernandez Romero J. A., 2015, TRENDS MICROBIOL, V23, P429

[18] Zinc Acetate/Carrageenan Gels Exhibit Potent Activity In Vivo against High-Dose Herpes Simplex Virus 2 Vaginal and Rectal Challenge [J].

Fernandez-Romero, Jose A. ;

Abraham, Ciby J. ;

Rodriguez, Aixa ;

Kizima, Larisa ;

Jean-Pierre, Ninochka ;

Menon, Radhika ;

Begay, Othell ;

Seidor, Samantha ;

Ford, Brian E. ;

Gil, Pedro I. ;

Peters, Jennifer ;

Katz, David ;

Robbiani, Melissa ;

Zydowsky, Thomas M. .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2012, 56 (01) :358-368

[19] Immune clearance of highly pathogenic SIV infection [J].

Hansen, Scott G. ;

Piatak, Michael, Jr. ;

Ventura, Abigail B. ;

Hughes, Colette M. ;

Gilbride, Roxanne M. ;

Ford, Julia C. ;

Oswald, Kelli ;

Shoemaker, Rebecca ;

Li, Yuan ;

Lewis, Matthew S. ;

Gilliam, Awbrey N. ;

Xu, Guangwu ;

Whizin, Nathan ;

Burwitz, Benjamin J. ;

Planer, Shannon L. ;

Turner, John M. ;

Legasse, Alfred W. ;

Axthelm, Michael K. ;

Nelson, Jay A. ;

Frueh, Klaus ;

Sacha, Jonah B. ;

Estes, Jacob D. ;

Keele, Brandon F. ;

Edlefsen, Paul T. ;

Lifson, Jeffrey D. ;

Picker, Louis J. .

NATURE, 2013, 502 (7469) :100-+

[20] Human papillomavirus infection and increased risk of HIV acquisition. A systematic review and meta-analysis [J].

Houlihan, Catherine F. ;

Larke, Natasha L. ;

Watson-Jones, Deborah ;

Smith-McCune, Karen K. ;

Shiboski, Stephen ;

Gravitt, Patti E. ;

Smith, Jennifer S. ;

Kuhn, Louise ;

Wang, Chunhui ;

Hayes, Richard .

AIDS, 2012, 26 (17) :2211-2222

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