SELECTION OF A MATHEMATICAL MODEL FOR THE KINETICS OF Haemophilus influenzae TYPE B USING AKAIKE’S INFORMATION CRITERION

ABSTRACT Haemophilus influenzae type b (Hib) vaccine is made up from its capsular polysaccharide (PRP). Low productivity of the polysaccharide during cell growth increases the final cost of this vaccine. Hib achieves low levels of cellular concentration in vitro due to the inhibition caused by acetate. The Akaike Information Criterion (AIC) was used in this work for selecting models of microbial growth. The application to the case of the multivariate models is outlined and the procedure is carried out using data from Hib cultures. From 4 models of biomass and 15 of acetate and PRP, one could be selected with great evidence for support. The use of AIC has shown to be robust and free of subjectivity, and it was able to define a kinetic model that is adequate for the cell growth and the production of its PRP over a wide range of culture conditions. The exponential inhibition factor was found to be the best for modelling inhibition of cell growth by acetate, while the hyperbolic factor was the best for inhibition of PRP formation. The acetate formation was found to have both growth associated and non-associated types. PRP formation was found to be only growth associated.

摘要：b型流感嗜血杆菌（Haemophilus influenzae type b, Hib）疫苗由其荚膜多糖（capsular polysaccharide, PRP）制备而成。该多糖在细胞生长过程中产量偏低，进而推高了这款疫苗的最终生产成本。体外培养条件下，乙酸盐产生的抑制作用会导致Hib的细胞浓度处于较低水平。本研究采用赤池信息准则（Akaike Information Criterion, AIC）筛选微生物生长模型，概述了其在多变量模型中的应用流程，并借助Hib培养数据集完成了具体建模步骤。研究从4个生物量模型、15个乙酸盐与PRP模型中，筛选出了具备强支撑证据的最优模型。结果表明，AIC的应用具备稳健性且不受主观因素影响，能够在宽泛的培养条件范围内，构建出适配Hib细胞生长与PRP合成的动力学模型。其中，指数抑制因子最适合用于模拟乙酸盐对细胞生长的抑制作用，而双曲抑制因子则更适用于描述乙酸盐对PRP合成的抑制效果。此外，乙酸盐的生成同时兼具生长偶联与非生长偶联两种类型，而PRP的合成则仅为生长偶联型。