Kuipers Kirsten, van Selm Saskia, van Opzeeland Fred, Langereis Jeroen D, Verhagen Lilly M, Diavatopoulos Dimitri A, de Jonge Marien I
Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Center, Radboud Center for Infectious Diseases, Nijmegen, The Netherlands.
Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital Utrecht, Utrecht, The Netherlands.
Vaccine. 2017 Sep 18;35(39):5235-5241. doi: 10.1016/j.vaccine.2017.08.023. Epub 2017 Aug 17.
Vaccination has been one of the most successful strategies to reduce morbidity and mortality caused by respiratory infections. Recent evidence suggests that differences in the host genetic background and environmental factors may contribute to heterogeneity in the immune response to vaccination. During pre-clinical testing, vaccines are often evaluated in a single mouse inbred strain, which may not translate well to the heterogeneous human population. Here, we examined the influence of host genetic background on vaccine-induced protection against pneumococcal colonization in two commonly used inbred mouse strains, i.e. C57BL/6 and BALB/cas well as the F1 cross of these two strains. Groups of mice were vaccinated intranasally with a vaccine formulation containing a model pneumococcal antigen, i.e. pneumococcal surface protein A (PspA), adjuvanted with cholera toxin subunit B (CTB). Even in the absence of vaccination, differences in colonization density were observed between mouse strains. Although vaccination significantly reduced pneumococcal density in all mouse strains, differences were observed in the magnitude of protection. We therefore examined immunological parameters known to be involved in vaccine-induced mucosal clearance of S. pneumoniae. We found that PspA-specific IgG levels in nasal tissue differed between mouse strains, but in all cases it correlated significantly with a reduction in colonization. Furthermore, increased mucosal IL17A, but not IFNγ, IL10, or IL4, was found to be mouse strain specific. This suggests that the reduction of bacterial load may be accompanied by a Th17 response in all genetic backgrounds, although the cytokine dynamics may differ. Increased insight into the different immune mechanisms that affect pneumococcal carriage will contribute to development of future vaccines against S. pneumoniae.
疫苗接种一直是降低呼吸道感染所致发病率和死亡率最成功的策略之一。最近的证据表明，宿主遗传背景和环境因素的差异可能导致疫苗免疫反应的异质性。在临床前测试中，疫苗通常在单一近交系小鼠中进行评估，而这可能无法很好地类推到异质性的人类群体。在此，我们研究了宿主遗传背景对两种常用近交系小鼠（即C57BL/6和BALB/c）以及这两个品系的F1杂交后代中疫苗诱导的抗肺炎球菌定植保护作用的影响。给小鼠组经鼻接种含有模型肺炎球菌抗原（即肺炎球菌表面蛋白A，PspA）并佐以霍乱毒素B亚基（CTB）的疫苗制剂。即使在未接种疫苗的情况下，也观察到小鼠品系之间在定植密度上存在差异。尽管接种疫苗显著降低了所有小鼠品系中的肺炎球菌密度，但在保护程度上仍存在差异。因此，我们研究了已知参与疫苗诱导的肺炎链球菌黏膜清除的免疫学参数。我们发现，鼻组织中PspA特异性IgG水平在小鼠品系之间存在差异，但在所有情况下，它都与定植减少显著相关。此外，发现黏膜IL17A增加，但IFNγ、IL10或IL4未增加，且具有小鼠品系特异性。这表明，尽管细胞因子动态可能不同，但在所有遗传背景下，细菌载量的降低可能伴随着Th17反应。对影响肺炎球菌携带的不同免疫机制的深入了解将有助于未来抗肺炎链球菌疫苗的研发。
