Kuipers Kirsten, Jong Wouter S P, van der Gaast-de Jongh Christa E, Houben Diane, van Opzeeland Fred, Simonetti Elles, van Selm Saskia, de Groot Ronald, Koenders Marije I, Azarian Taj, Pupo Elder, van der Ley Peter, Langereis Jeroen D, Zomer Aldert, Luirink Joen, de Jonge Marien I
Laboratory of Pediatric Infectious Diseases, Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Abera Bioscience AB, Stockholm, Sweden.
Infect Immun. 2017 Sep 20;85(10). doi: 10.1128/IAI.00281-17. Print 2017 Oct.
Serotype-specific protection against is an important limitation of the current polysaccharide-based vaccines. To prevent serotype replacement, reduce transmission, and limit the emergence of new variants, it is essential to induce broad protection and restrict pneumococcal colonization. In this study, we used a prototype vaccine formulation consisting of lipopolysaccharide (LPS)-detoxified outer membrane vesicles (OMVs) from serovar Typhimurium displaying the variable N terminus of PspA (α1α2) for intranasal vaccination, which induced strong Th17 immunity associated with a substantial reduction of pneumococcal colonization. Despite the variable nature of this protein, a common major histocompatibility complex class (MHC-II) epitope was identified, based on prediction combined with screening, and was essential for interleukin-17 A (IL-17A)-mediated cross-reactivity and associated with cross protection. Based on 1,352 PspA sequences derived from a pneumococcal carriage cohort, this OMV-based vaccine formulation containing a single α1α2 type was estimated to cover 19.1% of strains, illustrating the potential of Th17-mediated cross protection.
针对特定血清型的保护是当前基于多糖的疫苗的一个重要局限性。为了防止血清型替换、减少传播并限制新变种的出现，诱导广泛的保护并限制肺炎球菌定植至关重要。在本研究中，我们使用了一种原型疫苗制剂，其由来自鼠伤寒血清型的脂多糖（LPS）解毒外膜囊泡（OMV）组成，展示PspA（α1α2）的可变N端用于鼻内接种，这诱导了与肺炎球菌定植大幅减少相关的强烈Th17免疫。尽管该蛋白具有可变性质，但基于预测结合筛选鉴定出了一个共同的主要组织相容性复合体II类（MHC-II）表位，它对于白细胞介素-17 A（IL-17A）介导的交叉反应性至关重要，并与交叉保护相关。基于来自肺炎球菌携带队列的1352个PspA序列，估计这种含有单一α1α2类型的基于OMV的疫苗制剂可覆盖19.1%的菌株，说明了Th17介导的交叉保护的潜力。
