Increasing role of herpes simplex virus type 1 in first-episode anogenital herpes in heterosexual women and younger men who have sex with men, 1992-2006

Ryder, Nathan; Jin, Fengyi; McNulty, Anna; Grulich, Andrew E.; Donovan, Basil

doi:10.1136/sti.2008.033902

Cited by 105 publications

(57 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The infectious dose required to induce genital disease and 100% mortality is substantially higher for HSV-1 than for HSV-2 (ϳ10 6 PFU/animal versus ϳ10 3 PFU/animal, respectively). The progression of genital herpes is very rapid for HSV-2, with mortality typically following lesion formation in 2 to 3 days or preceding any lesion detection.…”

Section: Discussionmentioning

confidence: 99%

“…Globally, HSV-2 is a major health threat, with 16% of the U.S. population infected by age 30 and 50 to 90% of the population in sub-Saharan Africa infected (3)(4)(5). Recent reports emphasize the importance of HSV-1 as an important etiologic agent of genital herpes particularly in the United States and other developed countries (6)(7)(8). Seroprevalence of HSV-1 among 14-to 49-year-olds in the United States reached 53.9% in 2005 to 2010 (5).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Efficacy of the Herpes Simplex Virus 2 (HSV-2) Glycoprotein D/AS04 Vaccine against Genital HSV-2 and HSV-1 Infection and Disease in the Cotton Rat Sigmodon hispidus Model

Boukhvalova

McKay

Mbaye

et al. 2015

J Virol

View full text Add to dashboard Cite

Subunit vaccines based on the herpes simplex virus 2 (HSV-2) glycoprotein D (gD-2) have been the major focus of HSV-2 vaccine development for the past 2 decades. Based on the promising data generated in the guinea pig model, a formulation containing truncated gD-2, aluminum salt, and MPL (gD/AS04) advanced to clinical trials. The results of these trials, however, were unexpected, as the vaccine protected against HSV-1 infection but not against HSV-2. To address this discrepancy, we developed a Depot medroxyprogesterone acetate (DMPA)-treated cotton rat Sigmodon hispidus model of HSV-2 and HSV-1 genital infection. The severity of HSV-1 genital herpes was less than that of HSV-2 genital herpes in cotton rats, and yet the model allowed for comparative evaluation of gD/AS04 immunogenicity and efficacy. Cotton rats were intramuscularly vaccinated using a prime boost strategy with gD/AS04 (Simplirix vaccine) or control vaccine formulation (hepatitis B vaccine FENDrix) and subsequently challenged intravaginally with HSV-2 or HSV-1. The gD/AS04 vaccine was immunogenic in cotton rats and induced serum IgG directed against gD-2 and serum HSV-2 neutralizing antibodies but failed to efficiently protect against HSV-2 disease or to decrease the HSV-2 viral load. However, gD/AS04 significantly reduced vaginal titers of HSV-1 and better protected animals against HSV-1 compared to HSV-2 genital disease. The latter finding is generally consistent with the clinical outcome of the Herpevac trial of Simplirix. Passive transfer of serum from gD/AS04-immunized cotton rats conferred stronger protection against HSV-1 genital disease. These findings suggest the need for alternative vaccine strategies and the identification of new correlates of protection. IMPORTANCEIn spite of the high health burden of genital herpes, there is still no effective intervention against the disease. The significant gap in knowledge on genital herpes pathogenesis has been further highlighted by the recent failure of GSK HSV-2 vaccine Simplirix (gD/AS04) to protect humans against HSV-2 and the surprising finding that the vaccine protected against HSV-1 genital herpes instead. In this study, we report that gD/AS04 has higher efficacy against HSV-1 compared to HSV-2 genital herpes in the novel DMPA-synchronized cotton rat model of HSV-1 and HSV-2 infection. The findings help explain the results of the Simplirix trial.T he disease burden associated with herpes simplex virus 2 (HSV-2) infection, an important cause of genital herpes worldwide, is high and presents an additional threat due to its association with an increased risk of HIV acquisition and transmission (1-3). Globally, HSV-2 is a major health threat, with 16% of the U.S. population infected by age 30 and 50 to 90% of the population in sub-Saharan Africa infected (3-5). Recent reports emphasize the importance of HSV-1 as an important etiologic agent of genital herpes particularly in the United States and other developed countries (6-8). Seroprevalence of HSV-1 among 14-to 49-year-olds in the Uni...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Efficacy of the Herpes Simplex Virus 2 (HSV-2) Glycoprotein D/AS04 Vaccine against Genital HSV-2 and HSV-1 Infection and Disease in the Cotton Rat Sigmodon hispidus Model

Boukhvalova

McKay

Mbaye

et al. 2015

J Virol

View full text Add to dashboard Cite

show abstract

“…11), and HSV-1 may also cause significant eye and brain disease, almost all HSV vaccine candidates reaching clinical trials have targeted HSV-2. As HSV-1 and HSV-2 have similar pathogenesis and host interactions, many of the concepts for development of an effective vaccine are likely relevant to both viruses.…”

Section: Introductionmentioning

confidence: 99%

HSV-2: in pursuit of a vaccine

Johnston

Koelle²,

Wald³

2011

J. Clin. Invest.

127

111

View full text Add to dashboard Cite

Herpes simplex virus type 2 (HSV-2) is one of the most prevalent sexually transmitted infections worldwide. In addition to recurrent genital ulcers, HSV-2 causes neonatal herpes, and it is associated with a 3-fold increased risk for HIV acquisition. Although many HSV-2 vaccines have been studied in animal models, few have reached clinical trials, and those that have been tested in humans were not consistently effective. Here, we review HSV-2 pathogenesis, with a focus on novel understanding of mucosal immunobiology of HSV-2, and vaccine efforts to date, in an attempt to stimulate thinking about future directions for development of effective prophylactic and therapeutic HSV-2 vaccines.

show abstract

“…erpes simplex virus type 2 (HSV-2) is the primary causative agent of genital herpes worldwide (1), but HSV-1, which is usually orally located, has been shown recently to be responsible for an increasing proportion of first episode HSV infections (2). HSV is the major cause of genital ulcers in the developed world (3).…”

mentioning

confidence: 99%

Theaflavin-3,3′-Digallate and Lactic Acid Combinations Reduce Herpes Simplex Virus Infectivity

Isaacs

2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The present study examined the efficacy of using multiple mechanisms as part of a topical microbicide to inactivate herpes simplex virus (HSV) by combining theaflavin-3,3=-digallate (TF-3) and lactic acid (LA) over the pH range of 4.0 to 5.7 to mimic conditions in the female reproductive tract. Six clinical isolates of HSV-2 and two clinical isolates of HSV-1 were almost completely inactivated when TF-3 (100 M) was present with LA over the pH range of 4.5 to 5.7, whereas four additional HSV-1 clinical isolates required TF-3 concentrations of 250 to 500 M for comparable virus titer reduction. LA (1%) alone at pH 4.0 reduced the titers of laboratory and clinical isolates of HSV-1 and HSV-2 by >5 log 10 , but most LA-dependent antiviral activity was lost at a pH of >4.5. When HSV-1 and HSV-2 were incubated at pH 4.0 without LA virus titers were not reduced. At pH 4.0, HSV-1 and HSV-2 titers were reduced 5 log 10 in 20 min by LA alone. TF-3 reduced HSV-2 titers by 5 log 10 in 20 to 30 min at pH 4.5, whereas HSV-1 required 60 min for comparable inactivation. Mixtures of TF-3 and LA stored at 37°C for 1 month at pH 4.0 to 5.7 maintained antiviral activity. Semen, but not cervical vaginal fluid, decreased LA-dependent antiviral activity at pH 4.0, but adding TF-3 to the mixture reduced HSV titers by 4 to 5 log 10 . These results indicate that a combination microbicide containing TF-3 and LA could reduce HSV transmission.

show abstract

Increasing role of herpes simplex virus type 1 in first-episode anogenital herpes in heterosexual women and younger men who have sex with men, 1992-2006

Cited by 105 publications

References 15 publications

Efficacy of the Herpes Simplex Virus 2 (HSV-2) Glycoprotein D/AS04 Vaccine against Genital HSV-2 and HSV-1 Infection and Disease in the Cotton Rat Sigmodon hispidus Model

Efficacy of the Herpes Simplex Virus 2 (HSV-2) Glycoprotein D/AS04 Vaccine against Genital HSV-2 and HSV-1 Infection and Disease in the Cotton Rat Sigmodon hispidus Model

HSV-2: in pursuit of a vaccine

Theaflavin-3,3′-Digallate and Lactic Acid Combinations Reduce Herpes Simplex Virus Infectivity

Contact Info

Product

Resources

About