Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine

Coxsackievirus B (CVB) enteroviruses are common pathogens that can cause acute and chronic myocarditis, dilated cardiomyopathy, aseptic meningitis, and they are hypothesized to be a causal factor in type 1 diabetes. The licensed enterovirus vaccines and those currently in clinical development are traditional inactivated or live attenuated vaccines. Even though these vaccines work well in the prevention of enterovirus diseases, new vaccine technologies, like virus-like particles (VLPs), can offer important advantages in the manufacturing and epitope engineering. We have previously produced VLPs for CVB3 and CVB1 in insect cells. Here, we describe the production of CVB3-VLPs with enhanced production yield and purity using an improved purification method consisting of tangential flow filtration and ion exchange chromatography, which is compatible with industrial scale production. We also resolved the CVB3-VLP structure by Cryo-Electron Microscopy imaging and single particle reconstruction. The VLP diameter is 30.9 nm on average, and it is similar to Coxsackievirus A VLPs and the expanded enterovirus cell-entry intermediate (the 135s particle), which is similar to 2 nm larger than the mature virion. High neutralizing and total IgG antibody levels, the latter being a predominantly Th2 type (IgG1) phenotype, were detected in C57BL/6J mice immunized with non-adjuvanted CVB3-VLP vaccine. The structural and immunogenic data presented here indicate the potential of this improved methodology to produce highly immunogenic enterovirus VLP-vaccines in the future.Peer reviewe

Approach to Multi-Timescale Optimization for Distributed Energy Resources Clusters Considering Flexibility Margin

The disordered access of massively distributed energy resources (DERs) brings great challenges to the operation stability of the power grid. This paper puts forward the concept of a cluster, which gathers DERs in large quantities, small capacities, dispersion and disorder to form a large, centralized and orderly whole, namely cluster, with certain incentive measures. In this paper, a multi-timescale optimization method of day-ahead planning and intra-day rolling optimization is proposed according to the characteristics of aggregated clusters and the requirements of China’s power grid architecture. Specifically, the day ahead model is proposed in two steps: the first step is to establish an optimization model with the goal of optimal fitting the target load curve and maximizing the utilization of DERs; The second step is to establish a potential game model considering the reasonable distribution of cluster benefits. Taking the minimum percentage of output correction of each cluster as the objective, considering the deviation of load forecasting and the deviation of day ahead instruction execution, an intra-day rolling optimization model is established. Finally, the application scenario of cluster participation in power grid auxiliary peak shaving is simulated and verified. The simulation results show that the cluster collaborative optimization method proposed in this paper can effectively reduce the load peak valley difference and maximize the use of cluster resources. The optimization tasks can be reasonably allocated while ensuring the stable and reliable operation of the power grid

Chemically activatable viral capsid functionalized for cancer targeting.

AimTo design a theranostic capsule using the virus-like nanoparticle of the hepatitis E virus modified to display breast cancer cell targeting functional group (LXY30).MethodsFive surface-exposed residues were mutated to cysteine to allow conjugation to maleimide-linked chemical groups via thiol-selective linkages. Engineered virus-like nanoparticles were then covalently conjugated to a breast cancer recognized ligand, LXY30 and an amine-coupled near-infrared fluorescence dye.ResultsLXY30-HEV VLP was checked for its binding and entry to a breast cancer cell line and for tumor targeting in vivo to breast cancer tissue in mice. The engineered virus-like nanoparticle not only targeted cancer cells, but also appeared immune silent to native hepatitis E virus antibodies due to epitope disruption at the antibody-binding site.ConclusionThese results demonstrate the production of a theranostic capsule suitable for cancer diagnostics and therapeutics based on surface modification of a highly stable virus-like nanoparticle

Chemically activatable viral capsid functionalized for cancer targeting

AIM: To design a theranostic capsule using the virus-like nanoparticle of the hepatitis E virus modified to display breast cancer cell targeting functional group (LXY30). METHODS: Five surface-exposed residues were mutated to cysteine to allow conjugation to maleimide-linked chemical groups via thiol-selective linkages. Engineered virus-like nanoparticles were then covalently conjugated to a breast cancer recognized ligand, LXY30 and an amine-coupled near-infrared fluorescence dye. RESULTS: LXY30-HEV VLP was checked for its binding and entry to a breast cancer cell line and for tumor targeting in vivo to breast cancer tissue in mice. The engineered virus-like nanoparticle not only targeted cancer cells, but also appeared immune silent to native hepatitis E virus antibodies due to epitope disruption at the antibody-binding site. CONCLUSION: These results demonstrate the production of a theranostic capsule suitable for cancer diagnostics and therapeutics based on surface modification of a highly stable virus-like nanoparticle