Contriving a chimeric polyvalent vaccine to prevent infections caused by herpes simplex virus (type-1 and type-2): an exploratory immunoinformatic approach

Abstract

Herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) cause a variety of infections including oral-facial infections, genital herpes, herpes keratitis, cutaneous infection and so on. To date, FDA-approved licensed HSV vaccine is not available yet. Hence, the study was conducted to identify and characterize an effective epitope based polyvalent vaccine against both types of Herpes Simplex Virus. The selected proteins were retrieved from ViralZone and assessed to design highly antigenic epitopes by binding analyses of the peptides with MHC class-I and class-II molecules, antigenicity screening, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking approach. The final vaccine was constructed by the combination of top CTL, HTL and BCL epitopes from each protein along with suitable adjuvant and linkers. Physicochemical and secondary structure analysis, disulfide engineering, molecular dynamic simulation and codon adaptation were further employed to develop a unique multi-epitope peptide vaccine. Docking analysis of the refined vaccine structure with different MHC molecules and human immune TLR-2 receptor demonstrated higher interaction. Complexed structure of the modeled vaccine and TLR-2 showed minimal deformability at molecular level. Moreover, translational potency and microbial expression of the modeled vaccine was analyzed with pET28a(+) vector for E. coli strain K12 and the vaccine constructs had no similarity with entire human proteome. The study enabled design of a novel chimeric polyvalent vaccine to confer broad range immunity against both HSV serotypes. However, further wet lab based research using model animals are highly recommended to experimentally validate our findings.

Communicated by Ramaswamy H. Sarma     

Effect of neurogenic acupoint cupping on high sensitive C-reactive protein and pain perception in female chronic pelvic pain: A randomized controlled trial

Objectives:To determine the effect of neurogenic acupoint dry cupping therapy on high sensitive C-reactive protein (hs-CRP) level, pain perception & intensity, and life impact of pelvic pain in women with chronic pelvic pain (CPP), with regard to the biological and neurophysiological impacts of dry cupping on acupoint.Methods:Thirty women with CPP were randomly divided into two equal groups; the study group received dry cupping on neurogenic acupoints plus lifestyle modifications for 8 weeks (n=15), while the control group received only lifestyle modifications for 8 weeks (n=15). Women were assessed pre- and post-rehabilitation program with the hs-CRP blood test, the short-form McGill Pain Questionnaire (SF-MPQ), and the pelvic pain impact questionnaire (PPIQ).Results:Comparing both groups post-treatment revealed that there were significant reductions in levels of hs-CRP, and scores of SF-MPQ & PPIQ (p<0.05) in the study group compared with the control group. Also, there were significant positive correlations between hs-CRP and both SF-MPQ “Visual Analogue Scale (VAS), Present Pain Intensity (PPI) index & Pain Rating Index (PRI)” and PPIQ (p<0.05).Conclusion:Neurogenic acupoint cupping therapy had significantly improving effects on the degree of inflammation, pain perception & intensity, and life impact of pelvic pain in women with CPP.     

Ecology of Compounding Disturbances: The Effects of Prescribed Burning After Clearcutting

Disturbance regimes in much of the boreal forest have shifted from wildfire to clearcutting over the last century, resulting in concerns for biodiversity. Because the boreal forest has evolved under a natural fire regimes, we hypothesized that application of prescribed burning (PB) after clearcutting would result in plant communities more similar to wildfire than clearcut only. However, because clearcutting + PB involves multiple disturbances in a short interval, we proposed an alternate hypothesis that clearcutting + PB would result in a species composition and trait assemblage that differ from those that develop after a single wildfire or clearcutting event. We determined species composition, diversity, and trait composition of 17 clearcut, 17 clearcut + PB, and 15 wildfire sites of jack pine (Pinus banksiana) dominated forests in northwestern Ontario, Canada 15–37 years after disturbance. Contrary to our primary hypothesis we found that clearcut + PB formed communities different from wildfire and clearcut, the latter two being similar. Clearcut + PB harbored more early successional species associated with seed banking, wind dispersal, deciduous foliage, and alien origin than wildfire or clearcut sites, which showed no specific trait associations. Taxonomic and trait analysis of clearcut + PB sites exhibited effects of compound disturbances, as observed after short-interval fires, supporting our alternate hypothesis. We concluded that PB after clearcutting formed plant communities significantly different from those developed either after clearcutting or wildfire alone. We attribute this community divergence to the compounding effects associated with the addition of prescribed fire to these previously disturbed forests.     

Application of creeping flow through a linearly absorbing slit filled with porous medium to diseased renal tubules

Biomechanics and Modeling in Mechanobiology - In this paper, we have discussed the flow of a Newtonian fluid through a slit filled with porous medium and linearly reabsorbing porous walls. The...