由疫苗接种诱导的IgG亚类的类型是疫苗效力的重要决定因素,因为IgG亚类在其生物学功能方面有所不同。这项研究的目的是确定遗传背景对疫苗诱导的IgG亚类的产生和持续时间的影响。IgG1,IgG2b,和针对白喉类毒素(DT)的IgG3滴度,百日咳毒素(PT),丝状血凝素(FHA),在来自用氢氧化铝佐剂的DTaP疫苗接种的28个不同的近交和野生来源的菌株的小鼠中测量百合肌动蛋白(Prn)。疫苗特异性IgG亚类应答的滴度和持续时间在小鼠品系之间是不同的,表明遗传因素促成了这种变异。使用统计关联来鉴定有助于抗体产生和寿命的潜在机制。该分析表明,指导抗体产生幅度的机制对IgG1是抗原依赖性的,但对IgG2b和IgG3是抗原非依赖性的。然而,驱动抗体滴度长寿的机制是不依赖抗原的IgG1,IgG2b,IgG3IgG1和IgG3滴度的比率鉴定了Th1和Th2倾向小鼠品系。与具有完整TLR4的C3H/HeOuJ小鼠相比,TLR4缺陷型C3H/HeJ小鼠具有增强的IgG1应答。这项工作表明,遗传背景对疫苗诱导的IgG1,IgG2b,和小鼠的IgG3滴度。
The type of IgG subclasses induced by vaccination is an important determinant of vaccine efficacy because the IgG subclasses vary in their biological function. The goal of this study was to determine the influence of the genetic background on the production and duration of vaccine-induced IgG subclasses. IgG1, IgG2b, and IgG3 titers against diphtheria toxoid (DT), pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (Prn) were measured in mice from 28 different inbred and wild-derived strains vaccinated with an aluminum hydroxide-adjuvanted DTaP vaccine. The titers and duration of vaccine-specific IgG subclass responses were different among mouse strains, indicating that genetic factors contribute to this variation. Statistical associations were used to identify potential mechanisms that contribute to antibody production and longevity. This analysis showed that the mechanisms guiding the magnitude of antibody production were antigen-dependent for IgG1 but antigen-independent for IgG2b and IgG3. However, the mechanisms driving the longevity of antibody titers were antigen-independent for IgG1, IgG2b, and IgG3. The ratio of IgG1 and IgG3 titers identified Th1 and Th2-prone mouse strains. TLR4-deficient C3H/HeJ mice had an enhanced IgG1 response compared with C3H/HeOuJ mice with intact TLR4. This work demonstrates that the genetic background contributes significantly to the magnitude and longevity of vaccine-induced IgG1, IgG2b, and IgG3 titers in mice.