scholarly journals Zinc Acetate/Carrageenan Gels Exhibit Potent ActivityIn Vivoagainst High-Dose Herpes Simplex Virus 2 Vaginal and Rectal Challenge

2011 ◽  
Vol 56 (1) ◽  
pp. 358-368 ◽  
Author(s):  
José A. Fernández-Romero ◽  
Ciby J. Abraham ◽  
Aixa Rodriguez ◽  
Larisa Kizima ◽  
Ninochka Jean-Pierre ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Zinc Acetate ◽  
Sexual Transmission ◽  
High Dose ◽  
Acetate Solution ◽  
Sexual Transmission Of Hiv ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

ABSTRACTTopical microbicides that block the sexual transmission of HIV and herpes simplex virus 2 (HSV-2) are desperately needed to reduce the incidence of HIV infections worldwide. Previously we completed phase 3 testing of the carrageenan-based gel Carraguard. Although the trial did not show that Carraguard is effective in preventing HIV transmission during vaginal sex, it did show that Carraguard is safe when used weekly for up to 2 years. Moreover, Carraguard hasin vitroactivity against human papillomavirus (HPV) and HSV-2 and favorable physical and rheological properties, which makes it a useful vehicle to deliver antiviral agents such as zinc acetate. To that end, we previously reported that a prototype zinc acetate carrageenan gel protects macaques against vaginal challenge with combined simian-human immunodeficiency virus reverse transcriptase (SHIV-RT). Herein, we report the safety and efficacy of a series of zinc acetate and/or carrageenan gels. The gels protected mice (75 to 85% survival;P< 0.001) against high-dose (106-PFU) HSV-2 vaginal or rectal challenge. In contrast, zinc acetate formulated in HEC (hydroxyethylcellulose; or the Universal Placebo) failed to protect mice against the high-dose vaginal HSV-2 challenge (similar to aqueous zinc acetate solution and the placebo controls). The gels were found to be effective spreading gels, exhibited limited toxicityin vitro, caused minimal damage to the architecture of the cervicovaginal and rectal mucosaein vivo, and induced no increased susceptibility to HSV-2 infection in a mouse model. Our results provide a strong rationale to further optimize and evaluate the zinc acetate/carrageenan gels for their ability to block the sexual transmission of HIV and HSV-2.

scholarly journals A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 InfectionIn Vivo

2013 ◽  
Vol 57 (8) ◽  
pp. 4001-4009 ◽  
Author(s):  
Jessica Kenney ◽  
Aixa Rodríguez ◽  
Larisa Kizima ◽  
Samantha Seidor ◽  
Radhika Menon ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Zinc Acetate ◽  
Potential Candidate ◽  
Content Type ◽  
Immunodeficiency Virus ◽  
Gel Treatment ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

ABSTRACTWe 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 vitrotoxicity to lactobacilli andCandida albicanswas 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 orC. albicansnor 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.

Herpes simplex virus and HIV: genital infection synergy and novel approaches to dual prevention

2012 ◽  
Vol 23 (9) ◽  
pp. 613-619 ◽  
Author(s):  
A R Thurman ◽  
G F Doncel
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Sexual Transmission ◽  
Topical Administration ◽  
Efficient Data ◽  
Sexual Transmission Of Hiv ◽  
Simplex Virus ◽  
Exposure Prophylaxis ◽  
Hiv 1

Sexual transmission of HIV-1, in the absence of co-factors, is poorly efficient. Data support that herpes simplex virus type-2 (HSV-2) may increase a woman's susceptibility to HIV-1. Potential mechanisms by which HSV-2 serves as an HIV-1 enhancing co-factor include (1) initiation of a clinical or subclinical mucosal inflammatory response, (2) alteration of innate mucosal immunity and (3) weakening or breaching the protective genital epithelia. No clinical trial has examined prevention of primary HSV-2 infection to eliminate the major morbidities of this recurrent disease and as a strategy to reduce HIV-1 transmission. Topical administration of potent antivirals can achieve local concentrations that are orders of magnitude higher than those obtained with oral administration. This paper reviews major advances in oral and topical pre-exposure prophylaxis of HIV-1 and HSV-2 and, based on these data, hypothesizes that simultaneous prevention of sexual acquisition of HSV-2 and HIV-1 via topical antiretroviral agents will have a synergistic impact on both epidemics.

Herpes Simplex Virus-2 May Increase Susceptibility of the Sexual Transmission of Hepatitis C

1995 ◽  
Vol 22 (4) ◽  
pp. 210-216 ◽  
Author(s):  
STEVEN SHEV ◽  
ANDERS WIDELL ◽  
TOMAS BERGSTRÖM ◽  
SVANTE HERMODSSON ◽  
ANNIKA LINDHOLM ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Hepatitis C ◽  
Herpes Simplex ◽  
Sexual Transmission ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

scholarly journals Rapid Viral Expansion and Short Drug Half-Life Explain the Incomplete Effectiveness of Current Herpes Simplex Virus 2-Directed Antiviral Agents

2013 ◽  
Vol 57 (12) ◽  
pp. 5820-5829 ◽  
Author(s):  
Joshua T. Schiffer ◽  
David A. Swan ◽  
Lawrence Corey ◽  
Anna Wald
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Half Life ◽  
Clinical Trial Data ◽  
Viral Production ◽  
Drug Concentrations ◽  
Genital Shedding ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

ABSTRACTThe nucleoside analogues acyclovir (ACV) and famciclovir (FCV) reduce the frequency and severity of herpes simplex virus 2 (HSV-2) genital shedding, yet despite their high potencyin vitroand a lack of induced drug resistance, frequent episodes of breakthrough mucosal shedding occur. We tested a published stochastic, spatial mathematical model of HSV-2 replication and spread, in concert with pharmacokinetic and pharmacodynamic equations, against virologic data from clinical trials of twice-daily acyclovir and famciclovir suppression. The model reproduced the key features of clinical trial data, including genital shedding episode rate, expansion and decay dynamics, and heterogeneous peak viral production and duration. In simulations, these agents shortened episode duration by limiting the extent of viral production by 1 to 2 log units and limiting the formation of secondary ulcers by ∼50%. However, drug concentrations were noninhibitory during 42% of the dosing cycle. Even if drug concentrations were high at episode initiation, prolonged episodes often ensued due to drug decay over ensuing hours and subsequent rebound of rapidly replicating HSV-2. The local CD8+T-cell density was more predictive of episode viral production (R2= 0.42) and duration (R2= 0.21) than the drug concentration at episode onset (R2= 0.14 and 0.05, respectively), though the model projected that an agent with an equivalent potency but a two times longer half-life would decrease shedding by 80% compared to that of standard twice-daily regimens. Therefore, long half-life is a key characteristic of any agent that might fully suppress HSV-2 reactivations.

An Interleukin 12 Adjuvanted Herpes Simplex Virus 2 DNA Vaccine Is More Protective Than a Glycoprotein D Subunit Vaccine in a High-Dose Murine Challenge Model

2017 ◽  
Vol 30 (3) ◽  
pp. 178-195 ◽  
Author(s):  
Kenneth C. Bagley ◽  
Jennifer A. Schwartz ◽  
Hanne Andersen ◽  
John H. Eldridge ◽  
Rong Xu ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Dna Vaccine ◽  
Subunit Vaccine ◽  
Interleukin 12 ◽  
High Dose ◽  
Glycoprotein D ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2 ◽  
D Subunit

scholarly journals In vitro anti-herpes simplex virus-2 activity of Salvia desoleana Atzei & V. Picci essential oil

PLoS ONE ◽  
2017 ◽  
Vol 12 (2) ◽  
pp. e0172322 ◽  
Author(s):  
Valeria Cagno ◽  
Barbara Sgorbini ◽  
Cinzia Sanna ◽  
Cecilia Cagliero ◽  
Mauro Ballero ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Essential Oil ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

scholarly journals B7 Costimulation Molecules Expressed from the Herpes Simplex Virus 2 Genome Rescue Immune Induction in B7-Deficient Mice

2007 ◽  
Vol 81 (22) ◽  
pp. 12200-12209 ◽  
Author(s):  
Lydia G. Thebeau ◽  
Sri P. Vagvala ◽  
Yee M. Wong ◽  
Lynda A. Morrison
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Challenge Virus ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

ABSTRACT The interaction between B7 costimulation molecules on antigen-presenting cells and CD28 on antigen-responsive T cells is essential for T-cell activation and maturation of immune responses to herpes simplex virus (HSV) infection. Vaccine-induced immune responses also depend upon adequate upregulation of B7 costimulation molecules, but this signal may be limiting for replication-defective virus vaccines. We investigated whether expression of B7 costimulation molecules by a prototypical replication-defective antiviral vaccine could enhance immune responses to the vaccine and whether B7-1 and B7-2 would be similarly effective. We altered an ICP8− replication-defective strain of HSV type 2 (HSV-2), 5BlacZ, to encode either murine B7-1 or B7-2. B7 molecule expression was detected on the surface of cells infected in vitro and at the RNA level in tissue of immunized mice. Immunization of B7-1/B7-2 knockout mice with B7-encoding virus modestly expanded the number of gamma interferon-producing T cells and significantly augmented class-switched HSV-specific antibody responses compared with the parental virus. Mice immunized with either B7-expressing virus showed less replication of challenge virus in the genital mucosa than mice immunized with 5BlacZ, markedly fewer signs of genital and neurological disease, and little weight loss. Virtually all mice immunized with B7-encoding virus survived challenge with a large dose of HSV-2, whereas most 5BlacZ-immunized mice succumbed to infection. These results indicate that protective immune responses can be enhanced by the inclusion of host B7 costimulation molecules in a prototypical replication-defective HSV vaccine against HSV-2 genital infection and that B7-1 and B7-2 induce immune responses with similar capacities to fight HSV-2 infection.

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