In silico analysis of an envelope domain III-based multivalent fusion protein as a potential dengue vaccine candidate

PURPOSE: Dengue virus infection is now a global problem. Currently, there is no licensed vaccine or proven antiviral treatment against this virus. All four serotypes (1-4) of dengue virus can infect human. An effective dengue vaccine should be tetravalent to induce protective immune responses against all four serotypes. Most of dengue vaccine candidates are monovalent, or in the form of physically mixed multivalent formulations. Recently envelope protein domain III of virus is considered as a vaccine candidate, which plays critical roles in the most important viral activities. Development of a tetravalent protein subunit vaccine is very important for equal induction of immune system and prevention of unbalanced immunity. Here, we have presented and used a rational approach to design a tetravalent dengue vaccine candidate. MATERIALS AND METHODS: We designed a multi domain antigen by fusing four consensus domain III sequences together with appropriate hydrophobic linkers and used several types of bioinformatics software and neural networks to predict structural and immunological properties of the designed tetravalent antigen. RESULTS: We designed a tetravalent protein (EDIIIF) based on domain III of dengue virus envelope protein. According to the results of the bioinformatics analysis, the constructed models for EDIIIF protein were structurally stable and potentially immunogenic. CONCLUSION: The designed tetravalent protein can be considered as a potential dengue vaccine candidate. The presented approach can be used for rational design and in silico evaluation of chimeric dengue vaccine candidates.

new technical approach to cancers of the cervical esophagus

Background: The aim of this study was to assess the possibility of a primary end-to-end pharyngoesophageal anastomosis after standard tumor resection of the cervical esophagus by acute Aexion of the neck

Methods: A total of 34 consecutive patients with primary cervical esophageal cancer, none having received prior radio-or chemotherapy, were treated by two methods based on intraoperative findings. In 18 patients, reconstruction after esophageal resection was carried out by the standard gastric pull-through technique [control group]. In 16 patients, acute flexion of the neck after tumor resection allowed for recon-struction by primary end-to-end pharyngoesophagostomy [experimental group]

Results: There was no operative mortality in either group. The mean operative time for the experimental group was about 50 minutes less compared to the control group. Self-limited postoperative anastomotic leakage in the neck was twice as common in the experimental group. Postoperative dysphagia was about three times as common in the experimental group [5 patients [31%]] compared to the control group [2 patients [11%]]

Conclusion: In selected cases, segmental resection of primary cervical esophageal cancers reconstructed by end-to-end pharyngoesoph-agostomy is technically feasible by bending the neck acutely forward during anastomosis and maintaining it in the Aexed position during a postoperative period of about 7 days. The advantages are reduced scope and duration of the operation. The downside is doubling of the frequency of postoperative cervical leakage