Intranasal immunization with a mixture of PspA and a Toll-like receptor agonist induces specific antibodies and enhances bacterial clearance in the airways of mice.
Intranasal immunization with a mixture of PspA and a Toll-like receptor agonist induces specific antibodies and enhances bacterial clearance in the airways of mice.
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使用 PspA 和 Toll 样受体激动剂的混合物进行鼻内免疫可诱导特异性抗体并增强小鼠气道中的细菌清除率。
DOI：
10.1016/j.vaccine.2009.03.055
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发表时间：
2009
期刊：
影响因子：
5.5
通讯作者：
K. Oishi
中科院分区：
文献类型：
--
作者：
Keita Oma;Jizi Zhao;H. Ezoe;Y. Akeda;S. Koyama;Ken J. Ishii;K. Kataoka;K. Oishi
为了开发一种有效的肺炎链球菌鼻疫苗，在小鼠中比较了一组Toll样受体（TLR）激动剂与肺炎球菌表面蛋白A（PspA）组合对诱导PspA特异性抗体和细菌清除的作用。用10μg TLR激动剂（TLR 2-4和9）和2.5μg PspA每周一次经鼻免疫小鼠，持续3周。与单独施用PspA的小鼠相比，在施用PspA加每种TLR激动剂的小鼠中发现气道中PspA特异性免疫球蛋白G（IgG）和伊加以及血浆中PspA特异性IgG的水平显著增加。在使用血清型3肺炎球菌菌株的亚致死性肺炎模型中，与细菌攻击后3小时单独施用PspA或单独施用磷酸盐缓冲盐水的小鼠相比，施用PspA加每种TLR激动剂的小鼠中小鼠肺中的细菌密度显著降低。类似地，在用血清型19 F菌株感染后1天，在施用PspA加上每种TLR激动剂的小鼠的鼻咽中发现增强的细菌清除。我们的数据表明，PspA加TLR激动剂鼻腔免疫诱导的PspA特异性抗体能够降低不同血清型肺炎球菌攻击后鼻咽和肺中的细菌负荷。尽管存在偏斜的Th 1/Th 2免疫应答，但用PspA加每种TLR激动剂进行鼻免疫对小鼠感染后3小时从肺和感染后1天从鼻咽的细菌清除的作用是等效的。
To develop an effective nasal vaccine for Streptococcus pneumoniae, the effects of a panel of Toll-like receptor (TLR) agonists in combination with pneumococcal surface protein A (PspA) on induction of PspA-specific antibodies and bacterial clearance were compared in mice. Mice were nasally immunized with 10μg of TLR agonist (TLR 2–4 and 9) and 2.5μg of PspA once per week for 3 weeks. Significantly increased levels of PspA-specific immunoglobulin G (IgG) and IgA in the airways and PspA-specific IgG in plasma were found in mice administered PspA plus each TLR agonist, compared with mice administered PspA alone. In a sub-lethal pneumonia model using a serotype 3 pneumococcal strain, bacterial density in the lungs of mice was significantly reduced in mice administered PspA plus each TLR agonist, compared with mice administered either PspA alone or phosphate-buffered saline alone 3h after bacterial challenge. Similarly, enhanced bacterial clearance was found in the nasopharynx of mice administered PspA plus each TLR agonist 1 day after infection with a serotype 19F strain. Our data suggest that PspA-specific antibody induced by nasal immunization with PspA plus TLR agonist is capable of reducing the bacterial load in both the nasopharynx and lungs after challenge with pneumococci with different serotypes. Despite the skewed Th1/Th2 immune responses, the effects of nasal immunization with PspA plus each TLR agonist on bacterial clearances from the lungs 3h after infection and from nasopharynx 1 day after infection in mice were equivalent.
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影响因子：
4.4
作者：
A. Yoshimura;E. Lien;R. Ingalls;E. Tuomanen;R. Dziarski;D. Golenbock
通讯作者：
A. Yoshimura;E. Lien;R. Ingalls;E. Tuomanen;R. Dziarski;D. Golenbock
DOI：
10.1073/pnas.250476497
发表时间：
2000-12-05
影响因子：
11.1
作者：
Ozinsky, A;Underhill, DM;Aderem, A
通讯作者：
Aderem, A
影响因子：
6.4
作者：
Briles, DE;Hollingshead, SK;Nabors, GS
通讯作者：
Nabors, GS
影响因子：
5.5
作者：
Nabors, GS;Braun, PA;Becker, RS
通讯作者：
Becker, RS
影响因子：
6.4
作者：
Briles, DE;Hollingshead, SK;Benjamin, WH
通讯作者：
Benjamin, WH