ACIDFORM inactivates herpes simplex virus and prevents genital herpes in a mouse model: Optimal candidate for microbicide combinations

Autores
Tuyama, Ana C. G.; Cheshenko, Natalia; Carlucci, Maria Josefina; Li, Jin Hua; Goldberg, Cindy L.; Waller, Donald P.; Anderson, Robert A.; Profy, Albert T.; Klotman, Mary E.; Keller, Maria J.; Herold, Betsy C.
Año de publicación
2006
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The acidic vaginal milieu is presumed to inactivate pathogens but is neutralized by semen. This notion fostered the development of acid-buffering products, such as ACIDFORM (developed by Program for Topical Prevention of Conception and Disease, Rush University, and licensed by Instead), as microbicides. However, the extent and mechanism of protective activity provided by buffering gels is not known. Exposure of herpes simplex virus (HSV) to pH 4.5 or lower irreversibly inactivated HSV and reduced HSV yields by at least 90%; exposure to pH 5.0 had little or no effect. Pretreatment of HSV-2 with pH 3.5-4.5 triggered proteolysis, disrupting the HSV particle and resulting in a reduction in binding and invasion. ACIDFORM protected 21 (81%) of 26 mice from genital herpes, compared with 3 (12%) of 25 mice who received a placebo gel. ACIDFORM retained significant activity if mice were challenged with HSV delivered in seminal fluid. These findings suggest that ACIDFORM offers considerable protection against HSV and may be an optimal candidate for developing combination microbicides.
Fil: Tuyama, Ana C. G.. Mount Sinai School of Medicine; Estados Unidos
Fil: Cheshenko, Natalia. Mount Sinai School of Medicine; Estados Unidos
Fil: Carlucci, Maria Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Mount Sinai School of Medicine; Estados Unidos
Fil: Li, Jin Hua. Mount Sinai School of Medicine; Estados Unidos
Fil: Goldberg, Cindy L.. Mount Sinai School of Medicine; Estados Unidos
Fil: Waller, Donald P.. University of Illinois; Estados Unidos
Fil: Anderson, Robert A.. Rush University; Argentina
Fil: Profy, Albert T.. Indevus Pharmaceuticals; Estados Unidos
Fil: Klotman, Mary E.. Mount Sinai School of Medicine; Estados Unidos
Fil: Keller, Maria J.. Mount Sinai School of Medicine; Estados Unidos
Fil: Herold, Betsy C.. Mount Sinai School of Medicine; Estados Unidos
Materia
MICROBICIDES
ANTIVIRAL
HERPES
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:11336/97784
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling ACIDFORM inactivates herpes simplex virus and prevents genital herpes in a mouse model: Optimal candidate for microbicide combinationsTuyama, Ana C. G.Cheshenko, NataliaCarlucci, Maria JosefinaLi, Jin HuaGoldberg, Cindy L.Waller, Donald P.Anderson, Robert A.Profy, Albert T.Klotman, Mary E.Keller, Maria J.Herold, Betsy C.MICROBICIDESANTIVIRALHERPEShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The acidic vaginal milieu is presumed to inactivate pathogens but is neutralized by semen. This notion fostered the development of acid-buffering products, such as ACIDFORM (developed by Program for Topical Prevention of Conception and Disease, Rush University, and licensed by Instead), as microbicides. However, the extent and mechanism of protective activity provided by buffering gels is not known. Exposure of herpes simplex virus (HSV) to pH 4.5 or lower irreversibly inactivated HSV and reduced HSV yields by at least 90%; exposure to pH 5.0 had little or no effect. Pretreatment of HSV-2 with pH 3.5-4.5 triggered proteolysis, disrupting the HSV particle and resulting in a reduction in binding and invasion. ACIDFORM protected 21 (81%) of 26 mice from genital herpes, compared with 3 (12%) of 25 mice who received a placebo gel. ACIDFORM retained significant activity if mice were challenged with HSV delivered in seminal fluid. These findings suggest that ACIDFORM offers considerable protection against HSV and may be an optimal candidate for developing combination microbicides.Fil: Tuyama, Ana C. G.. Mount Sinai School of Medicine; Estados UnidosFil: Cheshenko, Natalia. Mount Sinai School of Medicine; Estados UnidosFil: Carlucci, Maria Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Mount Sinai School of Medicine; Estados UnidosFil: Li, Jin Hua. Mount Sinai School of Medicine; Estados UnidosFil: Goldberg, Cindy L.. Mount Sinai School of Medicine; Estados UnidosFil: Waller, Donald P.. University of Illinois; Estados UnidosFil: Anderson, Robert A.. Rush University; ArgentinaFil: Profy, Albert T.. Indevus Pharmaceuticals; Estados UnidosFil: Klotman, Mary E.. Mount Sinai School of Medicine; Estados UnidosFil: Keller, Maria J.. Mount Sinai School of Medicine; Estados UnidosFil: Herold, Betsy C.. Mount Sinai School of Medicine; Estados UnidosOxford University Press2006-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/97784Tuyama, Ana C. G.; Cheshenko, Natalia; Carlucci, Maria Josefina; Li, Jin Hua; Goldberg, Cindy L.; et al.; ACIDFORM inactivates herpes simplex virus and prevents genital herpes in a mouse model: Optimal candidate for microbicide combinations; Oxford University Press; Journal Of Infectious Diseases; 194; 6; 9-2006; 795-8030022-1899CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1086/506948info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jid/article/194/6/795/865061info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:47:58Zoai:ri.conicet.gov.ar:11336/97784instacron: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 14:47:59.035CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv ACIDFORM inactivates herpes simplex virus and prevents genital herpes in a mouse model: Optimal candidate for microbicide combinations
title ACIDFORM inactivates herpes simplex virus and prevents genital herpes in a mouse model: Optimal candidate for microbicide combinations
spellingShingle ACIDFORM inactivates herpes simplex virus and prevents genital herpes in a mouse model: Optimal candidate for microbicide combinations
Tuyama, Ana C. G.
MICROBICIDES
ANTIVIRAL
HERPES
title_short ACIDFORM inactivates herpes simplex virus and prevents genital herpes in a mouse model: Optimal candidate for microbicide combinations
title_full ACIDFORM inactivates herpes simplex virus and prevents genital herpes in a mouse model: Optimal candidate for microbicide combinations
title_fullStr ACIDFORM inactivates herpes simplex virus and prevents genital herpes in a mouse model: Optimal candidate for microbicide combinations
title_full_unstemmed ACIDFORM inactivates herpes simplex virus and prevents genital herpes in a mouse model: Optimal candidate for microbicide combinations
title_sort ACIDFORM inactivates herpes simplex virus and prevents genital herpes in a mouse model: Optimal candidate for microbicide combinations
dc.creator.none.fl_str_mv Tuyama, Ana C. G.
Cheshenko, Natalia
Carlucci, Maria Josefina
Li, Jin Hua
Goldberg, Cindy L.
Waller, Donald P.
Anderson, Robert A.
Profy, Albert T.
Klotman, Mary E.
Keller, Maria J.
Herold, Betsy C.
author Tuyama, Ana C. G.
author_facet Tuyama, Ana C. G.
Cheshenko, Natalia
Carlucci, Maria Josefina
Li, Jin Hua
Goldberg, Cindy L.
Waller, Donald P.
Anderson, Robert A.
Profy, Albert T.
Klotman, Mary E.
Keller, Maria J.
Herold, Betsy C.
author_role author
author2 Cheshenko, Natalia
Carlucci, Maria Josefina
Li, Jin Hua
Goldberg, Cindy L.
Waller, Donald P.
Anderson, Robert A.
Profy, Albert T.
Klotman, Mary E.
Keller, Maria J.
Herold, Betsy C.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv MICROBICIDES
ANTIVIRAL
HERPES
topic MICROBICIDES
ANTIVIRAL
HERPES
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The acidic vaginal milieu is presumed to inactivate pathogens but is neutralized by semen. This notion fostered the development of acid-buffering products, such as ACIDFORM (developed by Program for Topical Prevention of Conception and Disease, Rush University, and licensed by Instead), as microbicides. However, the extent and mechanism of protective activity provided by buffering gels is not known. Exposure of herpes simplex virus (HSV) to pH 4.5 or lower irreversibly inactivated HSV and reduced HSV yields by at least 90%; exposure to pH 5.0 had little or no effect. Pretreatment of HSV-2 with pH 3.5-4.5 triggered proteolysis, disrupting the HSV particle and resulting in a reduction in binding and invasion. ACIDFORM protected 21 (81%) of 26 mice from genital herpes, compared with 3 (12%) of 25 mice who received a placebo gel. ACIDFORM retained significant activity if mice were challenged with HSV delivered in seminal fluid. These findings suggest that ACIDFORM offers considerable protection against HSV and may be an optimal candidate for developing combination microbicides.
Fil: Tuyama, Ana C. G.. Mount Sinai School of Medicine; Estados Unidos
Fil: Cheshenko, Natalia. Mount Sinai School of Medicine; Estados Unidos
Fil: Carlucci, Maria Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Mount Sinai School of Medicine; Estados Unidos
Fil: Li, Jin Hua. Mount Sinai School of Medicine; Estados Unidos
Fil: Goldberg, Cindy L.. Mount Sinai School of Medicine; Estados Unidos
Fil: Waller, Donald P.. University of Illinois; Estados Unidos
Fil: Anderson, Robert A.. Rush University; Argentina
Fil: Profy, Albert T.. Indevus Pharmaceuticals; Estados Unidos
Fil: Klotman, Mary E.. Mount Sinai School of Medicine; Estados Unidos
Fil: Keller, Maria J.. Mount Sinai School of Medicine; Estados Unidos
Fil: Herold, Betsy C.. Mount Sinai School of Medicine; Estados Unidos
description The acidic vaginal milieu is presumed to inactivate pathogens but is neutralized by semen. This notion fostered the development of acid-buffering products, such as ACIDFORM (developed by Program for Topical Prevention of Conception and Disease, Rush University, and licensed by Instead), as microbicides. However, the extent and mechanism of protective activity provided by buffering gels is not known. Exposure of herpes simplex virus (HSV) to pH 4.5 or lower irreversibly inactivated HSV and reduced HSV yields by at least 90%; exposure to pH 5.0 had little or no effect. Pretreatment of HSV-2 with pH 3.5-4.5 triggered proteolysis, disrupting the HSV particle and resulting in a reduction in binding and invasion. ACIDFORM protected 21 (81%) of 26 mice from genital herpes, compared with 3 (12%) of 25 mice who received a placebo gel. ACIDFORM retained significant activity if mice were challenged with HSV delivered in seminal fluid. These findings suggest that ACIDFORM offers considerable protection against HSV and may be an optimal candidate for developing combination microbicides.
publishDate 2006
dc.date.none.fl_str_mv 2006-09
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/11336/97784
Tuyama, Ana C. G.; Cheshenko, Natalia; Carlucci, Maria Josefina; Li, Jin Hua; Goldberg, Cindy L.; et al.; ACIDFORM inactivates herpes simplex virus and prevents genital herpes in a mouse model: Optimal candidate for microbicide combinations; Oxford University Press; Journal Of Infectious Diseases; 194; 6; 9-2006; 795-803
0022-1899
CONICET Digital
CONICET
url http://hdl.handle.net/11336/97784
identifier_str_mv Tuyama, Ana C. G.; Cheshenko, Natalia; Carlucci, Maria Josefina; Li, Jin Hua; Goldberg, Cindy L.; et al.; ACIDFORM inactivates herpes simplex virus and prevents genital herpes in a mouse model: Optimal candidate for microbicide combinations; Oxford University Press; Journal Of Infectious Diseases; 194; 6; 9-2006; 795-803
0022-1899
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1086/506948
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jid/article/194/6/795/865061
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
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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
_version_ 1846082998000156672
score 13.216834

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