A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vi...

Autores
Kenney, Jessica; Rodríguez, Aixa; Kizima, Larisa; Seidor, Samantha; Menon, Radhika; Jean Pierre, Ninochka; Pugach, Pavel; Levendosky, Keith; Derby, Nina; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D.; Paglini, Maria Gabriela; Zydowsky, Thomas M.; Robbiani, Melissa; Fernández Romero, José A.
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We previously showed that a prototype gel comprising zinc acetate (ZA) in carrageenan (CG) protected mice against vaginal and rectal herpes simplex virus 2 (HSV-2) challenge as well as macaques against vaginal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) challenge. In this work, we modified buffers and cosolvents to obtain a stable, nearly iso-osmolal formulation and evaluated its safety and efficacy against SHIV-RT and HSV-2. In vitro toxicity to lactobacilli and Candida albicans was determined. Macaques were given daily doses of ZA and CG (ZA/CG) or CG alone vaginally for 14 days and challenged with SHIV-RT 24 h later. Mice were challenged vaginally or rectally with HSV-2 immediately after a single gel treatment to measure efficacy or vaginally 12 h after daily gel treatment for 7 days to evaluate the gel's impact on susceptibility to HSV-2 infection. The modified ZA/CG neither affected the viability of lactobacilli or C. albicans nor enhanced vaginal HSV-2 infection after daily ZA/CG treatment. Vaginal SHIV-RT infection of macaques was reduced by 66% (P = 0.006) when macaques were challenged 24 h after the last dose of gel. We observed 60% to 80% uninfected mice after vaginal (P < 0.0001) and rectal (P = 0.008) high-dose HSV-2 challenge. The modified ZA/CG gel is safe and effective in animal models and represents a potential candidate to limit the transmission of HIV and HSV-2.
Fil: Kenney, Jessica. Center for Biomedical Research; Estados Unidos
Fil: Rodríguez, Aixa. Center for Biomedical Research; Estados Unidos
Fil: Kizima, Larisa. Center for Biomedical Research; Estados Unidos
Fil: Seidor, Samantha. Center for Biomedical Research; Estados Unidos
Fil: Menon, Radhika. Center for Biomedical Research; Estados Unidos
Fil: Jean Pierre, Ninochka. Center for Biomedical Research; Estados Unidos
Fil: Pugach, Pavel. Center for Biomedical Research; Estados Unidos
Fil: Levendosky, Keith. Center for Biomedical Research; Estados Unidos
Fil: Derby, Nina. Center for Biomedical Research; Estados Unidos
Fil: Gettie, Agegnehu. The Rockefeller University; Estados Unidos
Fil: Blanchard, James. University of Tulane; Estados Unidos
Fil: Piatak, Michael. Frederick National Laboratory for Cancer Research; Estados Unidos
Fil: Lifson, Jeffrey D.. Frederick National Laboratory for Cancer Research; Estados Unidos
Fil: Paglini, Maria Gabriela. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología; Argentina
Fil: Zydowsky, Thomas M.. Center for Biomedical Research; Estados Unidos
Fil: Robbiani, Melissa. Center for Biomedical Research; Estados Unidos
Fil: Fernández Romero, José A.. Center for Biomedical Research; Estados Unidos. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología; Argentina
Materia
MICROBICIDES
ZINC ACETATE
MACAQUES
SHIV-RT
HSV-2
MOUSE
VAGINAL
RECTAL
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/27229
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/27229
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In VivoKenney, JessicaRodríguez, AixaKizima, LarisaSeidor, SamanthaMenon, RadhikaJean Pierre, NinochkaPugach, PavelLevendosky, KeithDerby, NinaGettie, AgegnehuBlanchard, JamesPiatak, MichaelLifson, Jeffrey D.Paglini, Maria GabrielaZydowsky, Thomas M.Robbiani, MelissaFernández Romero, José A.MICROBICIDESZINC ACETATEMACAQUESSHIV-RTHSV-2MOUSEVAGINALRECTALhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3We previously showed that a prototype gel comprising zinc acetate (ZA) in carrageenan (CG) protected mice against vaginal and rectal herpes simplex virus 2 (HSV-2) challenge as well as macaques against vaginal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) challenge. In this work, we modified buffers and cosolvents to obtain a stable, nearly iso-osmolal formulation and evaluated its safety and efficacy against SHIV-RT and HSV-2. In vitro toxicity to lactobacilli and Candida albicans was determined. Macaques were given daily doses of ZA and CG (ZA/CG) or CG alone vaginally for 14 days and challenged with SHIV-RT 24 h later. Mice were challenged vaginally or rectally with HSV-2 immediately after a single gel treatment to measure efficacy or vaginally 12 h after daily gel treatment for 7 days to evaluate the gel's impact on susceptibility to HSV-2 infection. The modified ZA/CG neither affected the viability of lactobacilli or C. albicans nor enhanced vaginal HSV-2 infection after daily ZA/CG treatment. Vaginal SHIV-RT infection of macaques was reduced by 66% (P = 0.006) when macaques were challenged 24 h after the last dose of gel. We observed 60% to 80% uninfected mice after vaginal (P < 0.0001) and rectal (P = 0.008) high-dose HSV-2 challenge. The modified ZA/CG gel is safe and effective in animal models and represents a potential candidate to limit the transmission of HIV and HSV-2.Fil: Kenney, Jessica. Center for Biomedical Research; Estados UnidosFil: Rodríguez, Aixa. Center for Biomedical Research; Estados UnidosFil: Kizima, Larisa. Center for Biomedical Research; Estados UnidosFil: Seidor, Samantha. Center for Biomedical Research; Estados UnidosFil: Menon, Radhika. Center for Biomedical Research; Estados UnidosFil: Jean Pierre, Ninochka. Center for Biomedical Research; Estados UnidosFil: Pugach, Pavel. Center for Biomedical Research; Estados UnidosFil: Levendosky, Keith. Center for Biomedical Research; Estados UnidosFil: Derby, Nina. Center for Biomedical Research; Estados UnidosFil: Gettie, Agegnehu. The Rockefeller University; Estados UnidosFil: Blanchard, James. University of Tulane; Estados UnidosFil: Piatak, Michael. Frederick National Laboratory for Cancer Research; Estados UnidosFil: Lifson, Jeffrey D.. Frederick National Laboratory for Cancer Research; Estados UnidosFil: Paglini, Maria Gabriela. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología; ArgentinaFil: Zydowsky, Thomas M.. Center for Biomedical Research; Estados UnidosFil: Robbiani, Melissa. Center for Biomedical Research; Estados UnidosFil: Fernández Romero, José A.. Center for Biomedical Research; Estados Unidos. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología; ArgentinaAmerican Society for Microbiology2013-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/27229Kenney, Jessica; Rodríguez, Aixa; Kizima, Larisa; Seidor, Samantha; Menon, Radhika; et al.; A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 57; 8; 6-2013; 4001-40090066-4804CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.00796-13info:eu-repo/semantics/altIdentifier/url/http://aac.asm.org/content/57/8/4001info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3719770/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:59:43Zoai:ri.conicet.gov.ar:11336/27229instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:59:43.507CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo
title A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo
spellingShingle A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo
Kenney, Jessica
MICROBICIDES
ZINC ACETATE
MACAQUES
SHIV-RT
HSV-2
MOUSE
VAGINAL
RECTAL
title_short A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo
title_full A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo
title_fullStr A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo
title_full_unstemmed A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo
title_sort A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo
dc.creator.none.fl_str_mv Kenney, Jessica
Rodríguez, Aixa
Kizima, Larisa
Seidor, Samantha
Menon, Radhika
Jean Pierre, Ninochka
Pugach, Pavel
Levendosky, Keith
Derby, Nina
Gettie, Agegnehu
Blanchard, James
Piatak, Michael
Lifson, Jeffrey D.
Paglini, Maria Gabriela
Zydowsky, Thomas M.
Robbiani, Melissa
Fernández Romero, José A.
author Kenney, Jessica
author_facet Kenney, Jessica
Rodríguez, Aixa
Kizima, Larisa
Seidor, Samantha
Menon, Radhika
Jean Pierre, Ninochka
Pugach, Pavel
Levendosky, Keith
Derby, Nina
Gettie, Agegnehu
Blanchard, James
Piatak, Michael
Lifson, Jeffrey D.
Paglini, Maria Gabriela
Zydowsky, Thomas M.
Robbiani, Melissa
Fernández Romero, José A.
author_role author
author2 Rodríguez, Aixa
Kizima, Larisa
Seidor, Samantha
Menon, Radhika
Jean Pierre, Ninochka
Pugach, Pavel
Levendosky, Keith
Derby, Nina
Gettie, Agegnehu
Blanchard, James
Piatak, Michael
Lifson, Jeffrey D.
Paglini, Maria Gabriela
Zydowsky, Thomas M.
Robbiani, Melissa
Fernández Romero, José A.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv MICROBICIDES
ZINC ACETATE
MACAQUES
SHIV-RT
HSV-2
MOUSE
VAGINAL
RECTAL
topic MICROBICIDES
ZINC ACETATE
MACAQUES
SHIV-RT
HSV-2
MOUSE
VAGINAL
RECTAL
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv We previously showed that a prototype gel comprising zinc acetate (ZA) in carrageenan (CG) protected mice against vaginal and rectal herpes simplex virus 2 (HSV-2) challenge as well as macaques against vaginal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) challenge. In this work, we modified buffers and cosolvents to obtain a stable, nearly iso-osmolal formulation and evaluated its safety and efficacy against SHIV-RT and HSV-2. In vitro toxicity to lactobacilli and Candida albicans was determined. Macaques were given daily doses of ZA and CG (ZA/CG) or CG alone vaginally for 14 days and challenged with SHIV-RT 24 h later. Mice were challenged vaginally or rectally with HSV-2 immediately after a single gel treatment to measure efficacy or vaginally 12 h after daily gel treatment for 7 days to evaluate the gel's impact on susceptibility to HSV-2 infection. The modified ZA/CG neither affected the viability of lactobacilli or C. albicans nor enhanced vaginal HSV-2 infection after daily ZA/CG treatment. Vaginal SHIV-RT infection of macaques was reduced by 66% (P = 0.006) when macaques were challenged 24 h after the last dose of gel. We observed 60% to 80% uninfected mice after vaginal (P < 0.0001) and rectal (P = 0.008) high-dose HSV-2 challenge. The modified ZA/CG gel is safe and effective in animal models and represents a potential candidate to limit the transmission of HIV and HSV-2.
Fil: Kenney, Jessica. Center for Biomedical Research; Estados Unidos
Fil: Rodríguez, Aixa. Center for Biomedical Research; Estados Unidos
Fil: Kizima, Larisa. Center for Biomedical Research; Estados Unidos
Fil: Seidor, Samantha. Center for Biomedical Research; Estados Unidos
Fil: Menon, Radhika. Center for Biomedical Research; Estados Unidos
Fil: Jean Pierre, Ninochka. Center for Biomedical Research; Estados Unidos
Fil: Pugach, Pavel. Center for Biomedical Research; Estados Unidos
Fil: Levendosky, Keith. Center for Biomedical Research; Estados Unidos
Fil: Derby, Nina. Center for Biomedical Research; Estados Unidos
Fil: Gettie, Agegnehu. The Rockefeller University; Estados Unidos
Fil: Blanchard, James. University of Tulane; Estados Unidos
Fil: Piatak, Michael. Frederick National Laboratory for Cancer Research; Estados Unidos
Fil: Lifson, Jeffrey D.. Frederick National Laboratory for Cancer Research; Estados Unidos
Fil: Paglini, Maria Gabriela. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología; Argentina
Fil: Zydowsky, Thomas M.. Center for Biomedical Research; Estados Unidos
Fil: Robbiani, Melissa. Center for Biomedical Research; Estados Unidos
Fil: Fernández Romero, José A.. Center for Biomedical Research; Estados Unidos. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología; Argentina
description We previously showed that a prototype gel comprising zinc acetate (ZA) in carrageenan (CG) protected mice against vaginal and rectal herpes simplex virus 2 (HSV-2) challenge as well as macaques against vaginal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) challenge. In this work, we modified buffers and cosolvents to obtain a stable, nearly iso-osmolal formulation and evaluated its safety and efficacy against SHIV-RT and HSV-2. In vitro toxicity to lactobacilli and Candida albicans was determined. Macaques were given daily doses of ZA and CG (ZA/CG) or CG alone vaginally for 14 days and challenged with SHIV-RT 24 h later. Mice were challenged vaginally or rectally with HSV-2 immediately after a single gel treatment to measure efficacy or vaginally 12 h after daily gel treatment for 7 days to evaluate the gel's impact on susceptibility to HSV-2 infection. The modified ZA/CG neither affected the viability of lactobacilli or C. albicans nor enhanced vaginal HSV-2 infection after daily ZA/CG treatment. Vaginal SHIV-RT infection of macaques was reduced by 66% (P = 0.006) when macaques were challenged 24 h after the last dose of gel. We observed 60% to 80% uninfected mice after vaginal (P < 0.0001) and rectal (P = 0.008) high-dose HSV-2 challenge. The modified ZA/CG gel is safe and effective in animal models and represents a potential candidate to limit the transmission of HIV and HSV-2.
publishDate 2013
dc.date.none.fl_str_mv 2013-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/27229
Kenney, Jessica; Rodríguez, Aixa; Kizima, Larisa; Seidor, Samantha; Menon, Radhika; et al.; A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 57; 8; 6-2013; 4001-4009
0066-4804
CONICET Digital
CONICET
url http://hdl.handle.net/11336/27229
identifier_str_mv Kenney, Jessica; Rodríguez, Aixa; Kizima, Larisa; Seidor, Samantha; Menon, Radhika; et al.; A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 57; 8; 6-2013; 4001-4009
0066-4804
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.00796-13
info:eu-repo/semantics/altIdentifier/url/http://aac.asm.org/content/57/8/4001
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3719770/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.216834

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