Dataset Information

Population level impact of an imperfect prophylactic vaccine for herpes simplex virus-2.

ABSTRACT: The continuation of developing Herpes simplex virus type-2 (HSV-2) prophylactic vaccines requires parallel mathematical modeling to quantify the effect on the population of these vaccines.Using mathematical modeling we derived 3 summary measures for the population effect of imperfect HSV-2 vaccines as a function of their efficacies in reducing susceptibility (VES), genital shedding (VEP), and infectivity during shedding (VEI). In addition, we studied the population level effect of vaccine intervention using representative vaccine efficacies.A vaccine with limited efficacy of reducing shedding frequency (VEP = 10%) and infectivity (VEI = 0%) would need to reduce susceptibility by 75% (VES = 75%) to substantially reduce the sustainability of HSV-2 infection in a population. No reduction in susceptibility would be required to reach this target in a vaccine that decreased shedding by 75% (VES = 0%, VEP = 75%, VEI = 0%). Mass vaccination using a vaccine with imperfect efficacies (VES = 30%, VEP = 75%, and VEI = 0%) in Kisumu, Kenya, in 2010 would decrease prevalence and incidence in 2020 by 7% and 30%, respectively. For lower prevalence settings, vaccination is predicted to have a lower effect on prevalence.A vaccine with substantially high efficacy of reducing HSV-2 shedding frequency would have a desirable effect at the population level. The vaccine's short-term impact in a high prevalence setting in Africa would be a substantial decrease in incidence, whereas its immediate impact on prevalence would be small and would increase slowly over time.

SUBMITTER: Alsallaq RA

PROVIDER: S-EPMC2860045 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Population level impact of an imperfect prophylactic vaccine for herpes simplex virus-2.

Alsallaq Ramzi A RA Schiffer Joshua T JT Longini Ira M IM Wald Anna A Corey Lawrence L Abu-Raddad Laith J LJ

Sexually transmitted diseases 20100501 5

<h4>Background</h4>The continuation of developing Herpes simplex virus type-2 (HSV-2) prophylactic vaccines requires parallel mathematical modeling to quantify the effect on the population of these vaccines.<h4>Methods</h4>Using mathematical modeling we derived 3 summary measures for the population effect of imperfect HSV-2 vaccines as a function of their efficacies in reducing susceptibility (VES), genital shedding (VEP), and infectivity during shedding (VEI). In addition, we studied the popula ...[more]

PMID: 20351622

Similar Datasets

Project description:BACKGROUND:Our objective was to assess the population-level association between herpes simplex virus 2 (HSV-2) and HIV prevalence. METHODS:Reports of HSV-2 and HIV prevalence were systematically reviewed and synthesized following PRISMA guidelines. Spearman rank correlation ((Equation is included in full-text article.)) was used to assess correlations. Risk ratios (RRHSV-2/HIV) and odds ratios (ORHSV-2/HIV) were used to assess HSV-2/HIV epidemiologic overlap. DerSimonian-Laird random-effects meta-analyses were conducted. RESULTS:In total, 939 matched HSV-2/HIV prevalence measures were identified from 77 countries. HSV-2 prevalence was consistently higher than HIV prevalence. Strong HSV-2/HIV prevalence association was found for all data ((Equation is included in full-text article.)?=?0.6, P?<?0.001), all data excluding people who inject drugs (PWID) and children ((Equation is included in full-text article.)?=?0.7, P?<?0.001), female sex workers ((Equation is included in full-text article.)?=?0.5, P?<?0.001), and MSM ((Equation is included in full-text article.)?=?0.7, P?<?0.001). No association was found for PWID ((Equation is included in full-text article.)?=?0.2, P?=?0.222) and children ((Equation is included in full-text article.)?=?0.3, P?=?0.082). A threshold effect was apparent where HIV prevalence was limited at HSV-2 prevalence less than 20%, but grew steadily with HSV-2 prevalence for HSV-2 prevalence greater than 20%. The overall pooled mean RRHSV-2/HIV was 5.0 (95% CI 4.7-5.3) and ORHSV-2/HIV was 9.0 (95% CI 8.4-9.7). The RRHSV-2/HIV and ORHSV-2/HIV showed similar patterns that conveyed inferences about HSV-2 and HIV epidemiology. CONCLUSION:HSV-2 and HIV prevalence are strongly associated. HSV-2 prevalence can be used as a proxy 'biomarker' of HIV epidemic potential, acting as a 'temperature scale' of the intensity of sexual risk behavior that drive HIV transmission. HSV-2 prevalence can be used to identify populations and/or sexual networks at high-risk of future HIV expansion, and help prioritization, optimization, and resource allocation of cost-effective prevention interventions.

Project description:Herpes simplex virus 1 (HSV-1) induces a profound host shutoff during lytic infection. The virion host shutoff (vhs) protein plays a key role in this process by efficiently cleaving host and viral mRNAs. Furthermore, the onset of viral DNA replication is accompanied by a rapid decline in host transcriptional activity. To dissect relative contributions of both mechanisms and elucidate gene-specific host transcriptional responses throughout the first 8 h of lytic HSV-1 infection, we used transcriptome sequencing of total, newly transcribed (4sU-labeled) and chromatin-associated RNA in wild-type (WT) and Δvhs mutant infection of primary human fibroblasts. Following virus entry, vhs activity rapidly plateaued at an elimination rate of around 30% of cellular mRNAs per hour until 8 h postinfection (p.i.). In parallel, host transcriptional activity dropped to 10 to 20%. While the combined effects of both phenomena dominated infection-induced changes in total RNA, extensive gene-specific transcriptional regulation was observable in chromatin-associated RNA and was surprisingly concordant between WT and Δvhs infections. Both induced strong transcriptional upregulation of a small subset of genes that were poorly expressed prior to infection but already primed by H3K4me3 histone marks at their promoters. Most interestingly, analysis of chromatin-associated RNA revealed vhs-nuclease-activity-dependent transcriptional downregulation of at least 150 cellular genes, in particular of many integrin adhesome and extracellular matrix components. This was accompanied by a vhs-dependent reduction in protein levels by 8 h p.i. for many of these genes. In summary, our study provides a comprehensive picture of the molecular mechanisms that govern cellular RNA metabolism during the first 8 h of lytic HSV-1 infection.IMPORTANCE The HSV-1 virion host shutoff (vhs) protein efficiently cleaves both host and viral mRNAs in a translation-dependent manner. In this study, we model and quantify changes in vhs activity, as well as virus-induced global loss of host transcriptional activity, during productive HSV-1 infection. In general, HSV-1-induced alterations in total RNA levels were dominated by these two global effects. In contrast, chromatin-associated RNA depicted gene-specific transcriptional changes. This revealed highly concordant transcriptional changes in WT and Δvhs infections, confirmed DUX4 as a key transcriptional regulator in HSV-1 infection, and identified vhs-dependent transcriptional downregulation of the integrin adhesome and extracellular matrix components. The latter explained seemingly gene-specific effects previously attributed to vhs-mediated mRNA degradation and resulted in a concordant loss in protein levels by 8 h p.i. for many of the respective genes.

Dataset Information

Population level impact of an imperfect prophylactic vaccine for herpes simplex virus-2.

Publications

Population level impact of an imperfect prophylactic vaccine for herpes simplex virus-2.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets