Effectiveness and Efficiency of Imperfect Therapeutic HSV-2 Vaccines

Schwartz, Ernest; Bodine, Erin; Blower, Sally

doi:10.4161/hv.4529

Cited by 17 publications

(31 citation statements)

References 32 publications

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“…Education about the virus transmission and safe sexual practices were demonstrated to be effective [39], [40]. These measures should be emphasized in younger population and the development of preventive measures should be implemented for the most vulnerable population including persons with weight problems and women.…”

Section: Discussionmentioning

confidence: 99%

Association between HSV1 Seropositivity and Obesity: Data from the National Health and Nutritional Examination Survey, 2007–2008

2011

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BackgroundHerpes simplex virus (HSV) is among the most common sexually transmitted pathogens in the United States and worldwide. HSV has a high incidence of undetected cases. In addition, there is no treatment, and there is a lack of knowledge why disparities among populations exist. Research studies suggest that fat tissue may participate in body's immune responses, and the impact of obesity on susceptibility to HSV1 infection is not clear. The purpose of this study was to examine whether obesity is a risk factor for HSV1 infection using a large sample from the general population.Methods/Principal FindingsThis cross-sectional study used data from the National Health and Examination and Nutritional Examination Survey (NHANES) from 2007–2008. Variables, gender, age, race/ethnicity, marital status, education, poverty level, and diabetes represented potential confounders and were included in analyses. The two-tailed Pearson's chi square, student's t test, and a multiple logistic regression analysis were applied to evaluate associations using a significance value of p≤0.05. Adjusted odds ratios with 95% confidence interval represented the degree of these associations. The prevalence of HSV1 infection in US population between 20 and 49 years old was 60.3% (n = 1,536). In this study, having a BMI classified as the obese group (BMI 30–39.9) was significantly associated with HSV1 infection before [unadjusted OR = 1.74 (95% CI 1.20–2.51), p = 0.006] and after controlling for socio-demographic factors [adjusted OR = 1.50 (95%CI 1.06–2.13)], p = 0.026]. This association was stronger than three already established risk factors of age, female gender, and poverty level.Conclusions/SignificanceThis study provides evidence that obesity may play a role in the susceptibility to HSV1 infection. Findings from this study suggest that obesity should be considered when designing preventive measures for HSV1 infection. These results may also explain why some people acquire HSV1 infections and some do not. Further, these findings may justify an increased emphasis on the control and prevention of HSV1 transmission and other pathogens in overweight and obese populations.

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Section: Discussionmentioning

confidence: 99%

Association between HSV1 Seropositivity and Obesity: Data from the National Health and Nutritional Examination Survey, 2007–2008

2011

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“…Promising results were more recently obtained in Phase I/II clinical trials with a live-attenuated ICP0 deletion virus, ICP10DPK, which completely prevented recurrences in 37.5 and 43.5% of the vaccinated patients in two trials [53]. Further development and identification of therapeutic vaccine candidates are needed, but mathematical modeling supports the development of a therapeutic HSV vaccine, which could provide both a therapeutic and epidemic-level benefit [54]. …”

Section: New Drug Targetsmentioning

confidence: 99%

Novel approaches in fighting herpes simplex virus infections

Wilson¹,

Fakioglu²,

Herold³

2009

Expert Review of Anti-infective Therapy

101

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The development of novel strategies to eradicate herpes simplex virus (HSV) is a global public health priority. While acyclovir and related nucleoside analogues provide successful modalities for treatment and suppression, HSV remains highly prevalent worldwide and is a major cofactor fueling the HIV epidemic. HSV is the predominant cause of genital ulcerative disease, and neonatal and sporadic infectious encephalitis. Asymptomatic shedding, which occurs more frequently than previously appreciated, contributes to viral transmission. Acyclovir resistance may be problematic for immunocompromised patients and highlights the need for new safe and effective agents. Ideally, vaccines to prevent infection, drugs to inhibit the establishment of or reactivation from latency, or vaginal microbicides to prevent sexual and perinatal transmission are needed to control the epidemic. This review summarizes current therapeutic options and strategies in development. Keywords acyclovir; herpes simplex virus; microbicide; vaccineThe discovery of acyclovir (ACV), a nucleoside analogue that is selectively phosphorylated by herpes simplex virus (HSV) and inhibits viral replication by acting as a substrate for viral DNA polymerase, ushered in a new era in antiviral chemo therapy [1,2]. Despite the overwhelming success of ACV and related drugs, HSV remains a major global health problem, and is the leading cause of encephalitis and genital ulcerative disease, and a major cofactor for HIV infection. This reflects, in part, the ability of the virus to uniformly establish latency, reactivate frequently and to be horizontally and vertically transmitted during periods of

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“…There are basically eight different HSV-2 models that have been developed (Blower et al, 1998;Fisman et al, 2002;Garnett et al, 2004;Ghani and Aral, 2005;Korenromp et al, 2002;Newton and Kuder, 2000;Schinazi, 1999;White and Garnett, 1999), although some have been revised and adapted over time and applied to several different research questions (Blower, 2004;Blower and Ma, 2004;Freeman et al, 2006aFreeman et al, , 2006bGershengorn and Blower, 2000;Gershengorn et al, 2003;Orroth et al, 2006;Schwartz and Blower, 2005;Schwartz et al, 2007;White et al, 2004;Williams et al, 2007). There are some key differences between the model structures.…”

Section: Previous and Concurrent Hsv-2 Modelingmentioning

confidence: 97%

Dynamic Modeling of Herpes Simplex Virus Type-2 (HSV-2) Transmission: Issues in Structural Uncertainty

et al. 2009

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The sexually transmitted infection (STI) Herpes simplex virus type-2 (HSV-2) is of public health concern because it is a very common frequently unrecognized lifelong infection, which may facilitate HIV transmission. Within HIV/STI modeling, structural uncertainty has received less attention than parametric uncertainty. By merging the compartments of a "complex" model, a "simple" HSV-2 model is developed. Sexual interactions between female sex workers (FSWs) and clients are modeled using data from India. Latin Hypercube Sampling selects from parameter distributions and both models are run for each of the 10,000 parameter sets generated. Outputs are compared (except for 2,450 unrealistic simulations). The simple model is a good approximation to the complex model once the HSV-2 epidemic has reached 60% of the equilibrium prevalence (95% of the 7,550 runs produced <10% relative error). The simple model is a reduced version of the complex model that retains details implicitly. For late-stage epidemics, the simple model gives similar prevalence trends to the complex model. As HSV-2 epidemics in many populations are advanced, the simple model is accurate in most instances, although the complex model may be preferable for early epidemics. The analysis highlights the issue of structural uncertainty and the value of reducing complexity.

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Effectiveness and Efficiency of Imperfect Therapeutic HSV-2 Vaccines

Cited by 17 publications

References 32 publications

Association between HSV1 Seropositivity and Obesity: Data from the National Health and Nutritional Examination Survey, 2007–2008

Association between HSV1 Seropositivity and Obesity: Data from the National Health and Nutritional Examination Survey, 2007–2008

Novel approaches in fighting herpes simplex virus infections

Dynamic Modeling of Herpes Simplex Virus Type-2 (HSV-2) Transmission: Issues in Structural Uncertainty

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