Model-Based Design of Growth-Attenuated Viruses

Live-virus vaccines activate both humoral and cell-mediated immunity, require only a single boosting, and generally provide longer immune protection than killed or subunit vaccines. However, growth of live-virus vaccines must be attenuated to minimize their potential pathogenic effects, and mechanisms of attenuation by conventional serial-transfer viral adaptation are not well-understood. New methods of attenuation based on rational engineering of viral genomes may offer a potentially greater control if one can link defined genetic modifications to changes in virus growth. To begin to establish such links between genotype and growth phenotype, we developed a computer model for the intracellular growth of vesicular stomatitis virus (VSV), a well-studied, nonsegmented, negative-stranded RNA virus. Our model incorporated established regulatory mechanisms of VSV while integrating key wild-type infection steps: hijacking of host resources, transcription, translation, and replication, followed by assembly and release of progeny VSV particles. Generalization of the wild-type model to allow for genome rearrangements matched the experimentally observed attenuation ranking for recombinant VSV strains that altered the genome position of their nucleocapsid gene. Finally, our simulations captured previously reported experimental results showing how altering the positions of other VSV genes has the potential to attenuate the VSV growth while overexpressing the immunogenic VSV surface glycoprotein. Such models will facilitate the engineering of new live-virus vaccines by linking genomic manipulations to controlled changes in virus gene-expression and growth

Validation of an integrated service model, Health-RESPECT, for older patients in long-term care institution using information and communication technologies: protocol of a cluster randomised controlled trial

Introduction There is an increased healthcare need to manage institutionalised older patients owing to the ageing population. To overcome substantial future challenges, the Health-RESPECT (caRE Systems for Patients/Elderly with Coordinated care using icT), a new information and communication technologies based integrated management service model, was developed to provide effective management, enable consultation with distant professionals and share medical information between acute care hospitals and long-term care institutions. Methods and analysis A cluster randomised controlled trial will be conducted to examine the effectiveness of the Health-RESPECT in older patients with chronic diseases and their medical staff in charge. Intervention involves registration with simple comprehensive geriatric assessment, establishment of an individualised care plan for three chronic diseases (hypertension, diabetes and heart failure), medication and rehabilitation management, periodic video-conference and in-system assessment after intervention period. Primary outcomes are control levels of the three chronic diseases, adequacy of drug management and overall functional status. Patients will be assessed at before and after study period and 3 months after study ended. Analysis will be carried out with an intention-to-treat principle. In addition to evaluate intervention effects, clinical usability and economic evaluation will be assessed. Ethics and dissemination The study protocol was reviewed and approved by the Seoul National University Bundang Hospital Institutional Review Board. Study findings will be published in peer-reviewed journals