BackgroundVaccine-escaped hepatitis B virus (HBV) mutations occur within the “a” determinant area, which is located in the major hydrophilic region (MHR) of the hepatitis B surface antigen (HBsAg) protein. It is now well established that the common G145R mutation is highly capable of escaping from HBsAg immune recognition. However, the impacts of this mutation on the structure and immunogenic activity of HBsAg have been poorly investigated.ObjectivesThe present study analyzed the effects of the G145R mutation on the structure and immunogenic activity of the HBsAg.Materials and MethodsThree-dimensional (3D) structure of HBsAg for both the wild-type and G145R mutant were predicted and refined using several web tools. After quantitative evaluations, the effects of the G145R mutation on the secondary and 3D structures of the HBsAg were investigated. In parallel, the immunogenic activity of the wild-type and mutant HBsAg was also analyzed using a ClusPro docking server as well as the IEDB web tool. Further analyses were performed via molecular dynamics (MD) simulations using the GROMACS v5.0.2 simulation package.ResultsThe G145R mutation causes a considerable reduction in the immunogenic activity of the HBsAg through a conformational change in the HBsAg antigenic loops. This mutation inserts a new β-strand in the “a” determinant region of the HBsAg, leading to a reduced binding affinity to its monoclonal antibody, MAb12. The G145R mutation also increased the compactness and stability of the HBsAg by enhancing the rigidity of the “a” determinant.ConclusionsThese data will be beneficial for designing more advanced antibodies for the recognition of the HBsAg in diagnostics. In addition, the results of this study may assist in the design or development of more effective hepatitis B vaccines.
Context: Hepatitis B Virus expanded program on immunization (EPI) started on 1993 in Iran. Most surveys have assessed the level of response to vaccine by measuring the titers of anti-HBs. This meta-analysis aimed to summarize the Iranian published data on the rate of vaccine-responders versus non-responders. Moreover, the impact of variables such as age, gender, type of vaccine, etc. on the levels of responsiveness was evaluated. Evidence Acquisition: All published papers on this topic in Iranian and international journals with affiliation of "Iran" were reviewed using standard keywords up to 2014. We included our study to healthy participants with no previous HBV infection and who had already received a complete course of HB vaccine. The estimated prevalence and 95% confidence intervals in 28 eligible articles for HBV vaccine responders (anti-HBs > 10 IU/mL) and non-responders (10 <) were analyzed by random effect method due to between-study heterogeneity. Results: The age of subjects was between 6 months and 15 years old. Overall, 5991 (51.5%) were male and 4571 (48.5%) females. Overall, 80% were responders to vaccine versus 20% nonresponders. With increase in age, the number of responders to vaccine decreased significantly (P = 0.001). There was no strong difference between responders versus nonresponders to vaccine for gender, types of vaccine, ethnicity and living area.
Conclusions:The results arose from this meta-analysis highlighted the safety of vaccine and its effectiveness in stimulating immune response of vaccines, despite being different in generation, manufacturers and types. Moreover, there was no substantial difference between Iranian and other international investigations in the rate of nonresponsiveness to HBV vaccine.
After health sector evolution in 2013, there was an improvement in the quantity and quality of health resources in Iran, but not enough action was taken in resources allocation for burn patients. →What this article adds: Although solving the problems related to equality in the distribution of health resources is not easy, assessing this issue has a great impact on improving the policymaking procedures and allocating the health system resources. Inequality assessment and accurate estimation of the resources needed for burn patients can help reduce the direct and indirect costs of health care systems, patients, and households.
Management and treatment of chronic wounds remain a significant problem in clinical practice. Stem cell therapies are an important and promising approach for regenerative medicine because of their selfrenewal and differentiation potential. Mesenchymal stem cells (MSCs), a major cellular source for regeneration, are present in almost all tissues. The use of embryonic stem cells is morally controversial because of the need to nurture and destroy embryonic cells. Therefore, adult umbilical cord tissues are of particular importance as an alternative source of perinatal tissues. Wharton Jelly is a gelatinous connective tissue in the umbilical cord containing MSCs that can differentiate into osteogenic, adipose, chondrogenic, and other lineages. These cells do not express the MHC-II molecule and show immunomodulatory properties that make them viable for allogeneic and xenogenic transplants in cell therapy. Therefore, the umbilical cord, especially the part named Wharton's jelly, is an important and promising source of mesenchymal stem cells.
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