NIH小鼠模型在评价13价肺炎球菌结合疫苗免疫原性中的作用

Role of NIH mouse model in evaluating the immunogenicity of 13-valent pneumococcal conjugate vaccine

目的研究小鼠模型在评价13价肺炎球菌结合疫苗(pneumococcal conjugate vaccine,PCV)免疫原性中的作用。方法15批13价PCV免疫NIH小鼠,免疫3针后采血,检测血清抗不同血清型荚膜多糖IgG抗体的含量和调理吞噬杀菌抗体的水平。检测方法采用WHO推荐的ELISA和OPA。系统性比较IgG抗体含量和调理吞噬杀菌滴度之间的相关关系,包括组内相关关系和均值相关关系以及两者之间在统计学上的差异。结果①各型的组内相关性在每个组之间有所不同23F型OPA滴度与IgG抗体水平之间相关系数比较低,而且各组之间的差异均有统计学意义(P均<0.05);3型的相关系数比较高,而且与大部分血清型(如4、6A、6B、9V、14、18C、19F和23F型)之间的差异均有统计学意义(P均<0.05);而7F型和几乎所有的型(23F型除外)之间差异均无统计学意义(P均>0.05)。另外,方差分析结果表明,各型之间总体的差异有统计学意义(P<0.05)。②每组有13个血清型,其在各组之间的差异除了G7组与其他12组的差异有统计学意义之外,其他各组之间的差异几乎没有统计学意义(P均>0.05)。另外,方差分析结果表明,各组之间总体上差异无统计学意义(P=0.17,P>0.05)。③均值相关性和组内相关性的均值有一定的差异,除了5型,其他血清型的均值相关性都高于组内相关性的均值。④对每个组13个血清型的组内相关性与均值相关性之间进行统计学上的差异比较:除了7、8、11组,其余都是均值相关性高。结论对15个组的几何平均滴度(geometric mean titer,GMT)和几何平均ELISA单位(geometric mean ELISA unit,GMU)进行相关性分析,得到均值相关性,均值相关性与组内在各种情况下的差异,说明均值相关性在一定程度上消除了这种个体的影响,能够比较准确地反映OPA滴度与IgG水平之间的相关关系。NIH小鼠作为13价PCV血清学评价的动物模型,其血清的GMU和GMT都能够反映疫苗的免疫原性。

Objective To investigate the role of a NIH mouse model in evaluating the immunogenicity of 13-valent pneumococcal conjugate vaccine(PCV)immunization.Methods NIH mice were immunized with fifteen batches of 13PCV,serum were collected after the 3rd dose,the levels of serum IgG antibodies and opsonophagocitic titers against different types of capsularpolysaccharide were measured.The standard quantitative ELISA method for detecting IgG antibodies in serum and the method for opsonophagocitic assay were used.The correlations between IgG antibody levels and opsonophagocytic titers were systematically compared:including intra-group correlations and mean correlations as well as statistical differences between them.Results①The within-group correlations for each serotype differed between groups and the correlation coefficients between OPA titers and IgG content levels were low fot serotype 23F and staistically significant for all groups(P<0.05).The correlation coefficient was higher for serotype 3 and statistically signifi-cant for most serotypes(e.g.,serotypes 4,6A,6B,9V,14,18C,19F,23F);The differences between serotype 7F and almost all serotypes(except 23F)were not significant(P>0.05).②There were 13 serotypes in each group,and the differences between the groups were hardly statistically significant except for the statistically significant differences between the G7 group and the other 12 groups(all P>0.05).In addition,the results of ANOVA showed that the overall differences between the groups were not statistically significant(P=0.17,P>0.05).③The mean correlations and the mean values of the within-group correlations were somewhat different,except for serotype 5,where the mean correlations were higher than the mean values of the within-group correlations.④Statistical differences were compared between the within-group correlations and the mean correlations for the 13 types in each group:except for groups 7,8,and 11,all were high in the mean correlations.Conclusion While correlation analysis of GMT and GMU of 15 groups was performed to obtain mean correlation,the difference between the mean correlation and the group within each situation indicates that the mean correlation eliminates this individual effect to some extent and can reflect the correlation between OPA titer and IgG level more accurately.NIH mice as a 13-valent pneumococcal conjugate vaccine serological evaluation animal model,the GMU and GMT of its serum are able to reflect the immunogenicity of the vaccine.