A potent combination microbicide that targets SHIV-RT, HSV-2 and HPV.
Prevalent infection with human herpes simplex 2 (HSV-2) or human papillomavirus (HPV) is associated with increased human immunodeficiency virus (HIV) acquisition. Microbicides that target HIV as well as these sexually transmitted infections (STIs) may more effectively limit HIV incidence. Previously...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3989196?pdf=render |
| _version_ | 1811276663860756480 |
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| author | Larisa Kizima Aixa Rodríguez Jessica Kenney Nina Derby Olga Mizenina Radhika Menon Samantha Seidor Shimin Zhang Keith Levendosky Ninochka Jean-Pierre Pavel Pugach Guillermo Villegas Brian E Ford Agegnehu Gettie James Blanchard Michael Piatak Jeffrey D Lifson Gabriela Paglini Natalia Teleshova Thomas M Zydowsky Melissa Robbiani José A Fernández-Romero |
| author_facet | Larisa Kizima Aixa Rodríguez Jessica Kenney Nina Derby Olga Mizenina Radhika Menon Samantha Seidor Shimin Zhang Keith Levendosky Ninochka Jean-Pierre Pavel Pugach Guillermo Villegas Brian E Ford Agegnehu Gettie James Blanchard Michael Piatak Jeffrey D Lifson Gabriela Paglini Natalia Teleshova Thomas M Zydowsky Melissa Robbiani José A Fernández-Romero |
| author_sort | Larisa Kizima |
| collection | DOAJ |
| description | Prevalent infection with human herpes simplex 2 (HSV-2) or human papillomavirus (HPV) is associated with increased human immunodeficiency virus (HIV) acquisition. Microbicides that target HIV as well as these sexually transmitted infections (STIs) may more effectively limit HIV incidence. Previously, we showed that a microbicide gel (MZC) containing MIV-150, zinc acetate (ZA) and carrageenan (CG) protected macaques against simian-human immunodeficiency virus (SHIV-RT) infection and that a ZC gel protected mice against HSV-2 infection. Here we evaluated a modified MZC gel (containing different buffers, co-solvents, and preservatives suitable for clinical testing) against both vaginal and rectal challenge of animals with SHIV-RT, HSV-2 or HPV. MZC was stable and safe in vitro (cell viability and monolayer integrity) and in vivo (histology). MZC protected macaques against vaginal (p<0.0001) SHIV-RT infection when applied up to 8 hours (h) prior to challenge. When used close to the time of challenge, MZC prevented rectal SHIV-RT infection of macaques similar to the CG control. MZC significantly reduced vaginal (p<0.0001) and anorectal (p = 0.0187) infection of mice when 10(6) pfu HSV-2 were applied immediately after vaginal challenge and also when 5×10(3) pfu were applied between 8 h before and 4 h after vaginal challenge (p<0.0248). Protection of mice against 8×10(6) HPV16 pseudovirus particles (HPV16 PsV) was significant for MZC applied up to 24 h before and 2 h after vaginal challenge (p<0.0001) and also if applied 2 h before or after anorectal challenge (p<0.0006). MZC provides a durable window of protection against vaginal infection with these three viruses and, against HSV-2 and HPV making it an excellent candidate microbicide for clinical use. |
| first_indexed | 2024-04-13T00:00:35Z |
| format | Article |
| id | doaj.art-9f20173b1dae4edd8e9a6f19a6dbcc8a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T00:00:35Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9f20173b1dae4edd8e9a6f19a6dbcc8a2022-12-22T03:11:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9454710.1371/journal.pone.0094547A potent combination microbicide that targets SHIV-RT, HSV-2 and HPV.Larisa KizimaAixa RodríguezJessica KenneyNina DerbyOlga MizeninaRadhika MenonSamantha SeidorShimin ZhangKeith LevendoskyNinochka Jean-PierrePavel PugachGuillermo VillegasBrian E FordAgegnehu GettieJames BlanchardMichael PiatakJeffrey D LifsonGabriela PagliniNatalia TeleshovaThomas M ZydowskyMelissa RobbianiJosé A Fernández-RomeroPrevalent infection with human herpes simplex 2 (HSV-2) or human papillomavirus (HPV) is associated with increased human immunodeficiency virus (HIV) acquisition. Microbicides that target HIV as well as these sexually transmitted infections (STIs) may more effectively limit HIV incidence. Previously, we showed that a microbicide gel (MZC) containing MIV-150, zinc acetate (ZA) and carrageenan (CG) protected macaques against simian-human immunodeficiency virus (SHIV-RT) infection and that a ZC gel protected mice against HSV-2 infection. Here we evaluated a modified MZC gel (containing different buffers, co-solvents, and preservatives suitable for clinical testing) against both vaginal and rectal challenge of animals with SHIV-RT, HSV-2 or HPV. MZC was stable and safe in vitro (cell viability and monolayer integrity) and in vivo (histology). MZC protected macaques against vaginal (p<0.0001) SHIV-RT infection when applied up to 8 hours (h) prior to challenge. When used close to the time of challenge, MZC prevented rectal SHIV-RT infection of macaques similar to the CG control. MZC significantly reduced vaginal (p<0.0001) and anorectal (p = 0.0187) infection of mice when 10(6) pfu HSV-2 were applied immediately after vaginal challenge and also when 5×10(3) pfu were applied between 8 h before and 4 h after vaginal challenge (p<0.0248). Protection of mice against 8×10(6) HPV16 pseudovirus particles (HPV16 PsV) was significant for MZC applied up to 24 h before and 2 h after vaginal challenge (p<0.0001) and also if applied 2 h before or after anorectal challenge (p<0.0006). MZC provides a durable window of protection against vaginal infection with these three viruses and, against HSV-2 and HPV making it an excellent candidate microbicide for clinical use.http://europepmc.org/articles/PMC3989196?pdf=render |
| spellingShingle | Larisa Kizima Aixa Rodríguez Jessica Kenney Nina Derby Olga Mizenina Radhika Menon Samantha Seidor Shimin Zhang Keith Levendosky Ninochka Jean-Pierre Pavel Pugach Guillermo Villegas Brian E Ford Agegnehu Gettie James Blanchard Michael Piatak Jeffrey D Lifson Gabriela Paglini Natalia Teleshova Thomas M Zydowsky Melissa Robbiani José A Fernández-Romero A potent combination microbicide that targets SHIV-RT, HSV-2 and HPV. PLoS ONE |
| title | A potent combination microbicide that targets SHIV-RT, HSV-2 and HPV. |
| title_full | A potent combination microbicide that targets SHIV-RT, HSV-2 and HPV. |
| title_fullStr | A potent combination microbicide that targets SHIV-RT, HSV-2 and HPV. |
| title_full_unstemmed | A potent combination microbicide that targets SHIV-RT, HSV-2 and HPV. |
| title_short | A potent combination microbicide that targets SHIV-RT, HSV-2 and HPV. |
| title_sort | potent combination microbicide that targets shiv rt hsv 2 and hpv |
| url | http://europepmc.org/articles/PMC3989196?pdf=render |
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