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     

The formation of amino acid precursors in the reaction of atomic carbon with water and ammonia at 77 K

When atomic carbon is condensed on a surface at 77 K containing ammonia and water, glycine, N-methylglycine, alanine, β-alanine, aspartic acid and serine are generated. It is postulated that these reactions may mimic those which occur when an extraterrestrial carbon atom condenses on a frozen surface coated with water and ammonia and may provide a route to extraterrestrial amino acids. Experiments designed to elucidate the mechanisms of amino acid formation under these conditions have been carried out.     

Effects of rat fetuin on stimulation of bone resorption in the presence of parathyroid hormone.

Rat fetuin, which is the rat counterpart of human alpha 2-HS glycoprotein and bovine fetuin, is only detectable in calcified tissues such as bone matrices and dentin, and bone cells such as osteoblasts and osteocytes immunohistochemically. The effect of this protein on bone resorption was examined to study its physiological role in bone metabolism. Rat fetuin increased bone resorption in the presence of low concentrations of parathyroid hormone (PTH), but it had no activity on bone resorption without PTH. The increase in bone resorption by PTH and PTH plus rat fetuin was inhibited by the addition of chymostatin, an inhibitor for cathepsin L. Moreover, we found that when type I collagen from rat was preincubated with rat fetuin, the digestion of rat type I collagen by cathepsin L was increased. These findings suggest that rat fetuin present in bone matrix is important in bone resorption.     

Effectiveness of vector control methods for the control of cutaneous and visceral leishmaniasis: A meta-review

Elimination of visceral leishmaniasis (VL) in Southeast Asia and global control of cutaneous leishmaniasis (CL) and VL are priorities of the World Health Organization (WHO). But is the existing evidence good enough for public health recommendations? This meta-review summarises the available and new evidence for vector control with the aims of establishing what is known about the value of vector control for the control of CL and VL, establishing gaps in knowledge, and particularly focusing on key recommendations for further scientific work. This meta-review follows the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) criteria, including (1) systematic reviews and meta-analyses (SRs/MAs) for (2) vector control methods and strategies and (3) for the control of CL and/or VL. Nine SRs/MAs were included, with different research questions and inclusion/exclusion criteria. The methods analysed for vector control can be broadly classified into (1) indoor residual spraying (IRS); (2) insecticide-treated nets (ITNs; including insecticide-impregnated bednets); (3) insecticide-treated curtains (ITCs; including insecticide-treated house screening); (4) insecticide-treated bedsheets (ITSs) and insecticide-treated fabrics (ITFs; including insecticide-treated clothing) and (5) durable wall lining (treated with insecticides) and other environmental measures to protect the house; (6) control of the reservoir host; and (7) strengthening vector control operations through health education. The existing SRs/MAs include a large variation of different primary studies, even for the same specific research sub-question. Also, the SRs/MAs are outdated, using available information until earlier than 2018 only. Assessing the quality of the SRs/MAs, there is a considerable degree of variation. It is therefore very difficult to summarise the results of the available SRs/MAs, with contradictory results for both vector indices and—if available—human transmission data. Conclusions of this meta-review are that (1) existing SRs/MAs and their results make policy recommendations for evidence-based vector control difficult; (2) further work is needed to establish efficacy and community effectiveness of key vector control methods with specific SRs and MAs (3) including vector and human transmission parameters; and (4) attempting to conclude with recommendations in different transmission scenarios.     

Anterior gradient 2 increases long-chain fatty acid uptake via stabilizing FABP1 and facilitates lipid accumulation

Anterior gradient 2 (AGR2), a protein disulfide isomerase (PDI), is a well-established oncogene. Here, we found that Agr2^-/- mice had a decreased fat mass and hepatic and serum lipid levels compared with their wild-type littermates after fasting, and exhibited reduced high-fat diet (HFD)-induced fat accumulation. Transgenic mice overexpressing AGR2 (Agr2/Tg) readily gained fat weight on a HFD but not a normal diet. Proteomic analysis of hepatic samples from Agr2^-/- mice revealed that depletion of AGR2 impaired long-chain fatty acid uptake and activation but did not affect de novo hepatic lipogenesis. Further investigations led to the identification of several effector substrates, particularly fatty acid binding protein-1 (FABP1) as essential for the AGR2-mediated effects. AGR2 was coexpressed with FABP1, and knockdown of AGR2 resulted in a reduction in FABP1 stability. Physical interactions of AGR2 and FABP1 depended on the PDI motif in AGR2 and the formation of a disulfide bond between these two proteins. Overexpression of AGR2 but not a mutant AGR2 protein lacking PDI activity suppressed lipid accumulation in cells lacking FABP1. Moreover, AGR2 deficiency significantly reduced fatty acid absorption in the intestine, which might be resulted from decreased fatty acid transporter CD36 in mice. These findings demonstrated a novel role of AGR2 in fatty-acid uptake and activation in both the liver and intestine, which contributed to the AGR2-mediated lipid accumulation, suggesting that AGR2 is an important regulator of whole-body lipid metabolism and down-regulation of AGR2 may antagonize the development of obesity.