Study on the Problem of Multistage Vaccine Production and Allocation with Capacity Constraints

Vaccination is the best way to build an immune barrier to control a new infectious disease.Considering the limited production capacity at the initial stage of vaccine production,the problem of multistage vaccine production and allocation is studied under the policy of free treatment for infected patients by the government.Given the population and infection rates of different regions and the vaccine production capacity of each stage,an integer programming model is established to minimize the sum of production-and-vaccination cost and treatment cost of infected patients,which is solved by the GUROBI solver.The correctness of the model is verified by simulation,and the necessity of considering the treatment cost of infected patients in the objective function is further analyzed,which confirmed the correctness of the free treatment policy for patients in China.A heuristic algorithm is designed to solve the large-scale problem and numerical experiments are conducted to verify the efficiency of this algorithm.Furthermore,based on the sensitivity analysis results of parameters,the optimal vaccine production and allocation strategy are proposed,which provide the decision basis for the government departments to make reasonable vaccine production and vaccination plan.

A Deleted Deletion Site in a New Vector Strain and Exceptional Genomic Stability of Plaque-Purified Modified Vaccinia Ankara(MVA)

Vectored vaccines based on highly attenuated modified vaccinia Ankara(MVA) are reported to be immunogenic, tolerant to pre-existing immunity, and able to accommodate and stably maintain very large transgenes. MVA is usually produced on primary chicken embryo fibroblasts, but production processes based on continuous cell lines emerge as increasingly robust and cost-effective alternatives. An isolate of a hitherto undescribed genotype was recovered by passage of a nonplaque-purified preparation of MVA in a continuous anatine suspension cell line(CR.pIX) in chemically defined medium.The novel isolate(MVA-CR19) replicated to higher infectious titers in the extracellular volume of suspension cultures and induced fewer syncytia in adherent cultures. We now extend previous studies with the investigation of the point mutations in structural genes of MVA-CR19 and describe an additional point mutation in a regulatory gene. We furthermore map and discuss an extensive rearrangement of the left telomer of MVA-CR19 that appears to have occurred by duplication of the right telomer. This event caused deletions and duplications of genes that may modulate immunologic properties of MVACR19 as a vaccine vector. Our characterizations also highlight the exceptional genetic stability of plaque-purified MVA:although the phenotype of MVA-CR19 appears to be advantageous for replication, we found that all genetic markers that differentiate wildtype and MVA-CR19 are stably maintained in passages of recombinant viruses based on either wildtype or MVA-CR.