Neisseria meningitidis PorB, a Toll-like receptor 2 ligand, improves the capacity of Francisella tularensis lipopolysaccharide to protect mice against experimental tularemia
Neisseria meningitidis PorB, a Toll-like receptor 2 ligand, improves the capacity of Francisella tularensis lipopolysaccharide to protect mice against experimental tularemia
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DOI：
10.1128/cvi.00125-08
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发表时间：
2008-09-01
影响因子：
--
通讯作者：
Wetzler, Lee M.
中科院分区：
文献类型：
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作者：
Chiavolini, Damiana;Weir, Susan;Wetzler, Lee M.
图拉氏方济各氏菌会导致严重的肺炎，如果不加以治疗，可能会致命。由于其作为生物武器的潜在用途，目前正在进行研究，以开发有效的疫苗，并选择和研究能够产生更好和持久保护效果的佐剂分子。PorB是脑膜炎奈瑟菌的一种孔蛋白，是一种成熟的Toll样受体2配体，在体内外都能增强抗原提呈细胞的T细胞共刺激活性，是一种很有前途的疫苗佐剂候选分子。用图拉氏丝孢子虫亚种的脂多糖(LPS)免疫BALB/c小鼠。测定接种或不接种脑膜炎奈瑟氏菌PorB的霍尔卡氏菌活疫苗株(LVS)在免疫过程中的抗体水平和对LVS鼻腔攻击的保护力。单独注射抗原可诱导土拉氏杆菌脂多糖免疫球蛋白M(IgM)的特异性反应，但这种反应在数周内不会维持，仅对25%的小鼠有保护作用。相反，在整个免疫过程中，图拉氏杆菌脂多糖与新系列PorB联合免疫可诱导稳定的特异性IgM水平，并将存活小鼠的比例提高到70%。免疫后细胞因子分析显示，白细胞介素6(IL-6)、单核细胞趋化蛋白1和干扰素是死亡率的标志，而IL-1β与生存相关，与PorB作为佐剂的存在无关。这些数据表明，新系列PorB可能是提高图拉氏杆菌脂多糖和其他亚单位疫苗对图拉热的保护作用的最佳候选佐剂，但仍需测试其对A型和B型图拉氏杆菌强毒株的效力。
Francisella tularensis causes severe pneumonia that can be fatal if it is left untreated. Due to its potential use as a biological weapon, research is being conducted to develop an effective vaccine and to select and study adjuvant molecules able to generate a better and long-lasting protective effect. PorB, a porin from Neisseria meningitidis, is a well-established Toll-like receptor 2 ligand and has been shown to be a promising vaccine adjuvant candidate due to its ability to enhance the T-cell costimulatory activity of antigen-presenting cells both in vitro and in vivo. BALB/c mice were immunized with lipopolysaccharide (LPS) isolated from the F. tularensis subsp. holarctica live vaccine strain (LVS), with or without PorB from N. meningitidis, and the antibody levels induced during the vaccination regimen and the level of protection against intranasal challenge with LVS were determined. Antigen administered alone induced a specific F. tularensis LPS immunoglobulin M (IgM) response that was not maintained over the weeks and that conferred protection to only 25% of the mice. In contrast, F. tularensis LPS given in combination with neisserial PorB induced consistent levels of specific IgM throughout the immunization and increased the proportion of surviving mice to 70%. Postchallenge cytokine analysis showed that interleukin-6 (IL-6), monocyte chemoattractant protein 1, and gamma interferon were markers of mortality and that IL-1 beta was a correlate of survival, independent of the presence of PorB as an adjuvant. These data indicate that neisserial PorB might be an optimal candidate adjuvant for improving the protective effect of F. tularensis LPS and other subunit vaccines against tularemia, but there is still a need to test its efficacy against virulent type A and type B F. tularensis strains.