Active Immunization with Pneumolysin versus 23-Valent Polysaccharide Vaccine for Streptococcus pneumoniae Keratitis.
Active Immunization with Pneumolysin versus 23-Valent Polysaccharide Vaccine for Streptococcus pneumoniae Keratitis.
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DOI：
10.1167/iovs.10-6968
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发表时间：
2011-11
影响因子：
4.4
通讯作者：
Erin W. Norcross;M. Sanders;Quincy C. Moore;S. Taylor;Nathan A. Tullos;Rhonda R. Caston;S. N. Dixon;M. Nahm;R. Burton;H. Thompson;L. McDaniel;M. Marquart
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文献类型：
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作者：
Erin W. Norcross;M. Sanders;Quincy C. Moore;S. Taylor;Nathan A. Tullos;Rhonda R. Caston;S. N. Dixon;M. Nahm;R. Burton;H. Thompson;L. McDaniel;M. Marquart
本研究的目的是确定针对肺炎链球菌溶血素（Pneumolysin，Pneumolysin）或多糖胶囊的主动免疫是否对肺炎链球菌角膜炎相关的角膜损伤具有保护作用。方法新西兰白色兔在角膜感染10个菌落形成单位（CFU）的链球菌前，用混合肺炎链球菌溶血素类毒素（Pneumolysin toxoid，Pneumovax 23，PPSV 23; Merck，怀特豪斯站，NJ）的弗氏佐剂或磷酸盐缓冲液（PBS）主动免疫。肺炎。血清型特异性兔多克隆抗血清或模拟抗血清在静脉内感染10 CFU S之前被动给予兔。肺炎链球菌或角膜感染10 μ CFU。肺炎。结果主动免疫后48 h，用PSV 23和弗氏佐剂免疫的兔角膜临床评分明显低于PBS和弗氏佐剂及PSV 23和弗氏佐剂模拟免疫的兔角膜临床评分（P ≤ 0.0010），而用PPSV 23和弗氏佐剂免疫的兔与模拟免疫的兔相比在临床评分上没有显示出差异（P = 1.00）。来自用PPSV 23和弗氏佐剂主动免疫的兔的抗血清是非调理的。与模拟免疫兔相比，在WU 2感染后，从感染角膜中回收的细菌载量在经IPTG和PPSV 23免疫的兔中更高（P ≤ 0.007）。相反，在用K1443感染后，经K1443免疫的兔具有比对照兔更低的细菌载量（P = 0.0008）。IgG，伊加和IgM的定量在PLY免疫兔的血清中显示高浓度的PLY特异性IgG。此外，从ESPLY免疫的兔中纯化的抗ESPLY IgG中和ESPLY对人角膜上皮细胞的细胞溶解作用。被动施用能够调理和杀死S.肺炎链球菌对肺炎球菌菌血症有保护作用（P ≤ 0.05），但对角膜炎无保护作用（P ≥ 0.476）。结论肺炎球菌荚膜多糖和弗氏佐剂的主动免疫不能产生调理抗体，被动给予血清型特异性调理抗体对兔肺炎球菌角膜炎无保护作用，而保守蛋白毒力因子Ⅷ和弗氏佐剂的主动免疫能减轻肺炎球菌角膜炎相关的角膜炎症，但对角膜中的细菌负荷具有可变的影响。
PURPOSE The purpose of this study was to determine whether active immunization against pneumolysin (PLY), or polysaccharide capsule, protects against the corneal damage associated with Streptococcus pneumoniae keratitis. METHODS New Zealand White rabbits were actively immunized with Freund's adjuvant mixed with pneumolysin toxoid (ψPLY), Pneumovax 23 (PPSV23; Merck, Whitehouse Station, NJ), or phosphate-buffered saline (PBS), before corneal infection with 10⁵ colony-forming units (CFU) of S. pneumoniae. Serotype-specific rabbit polyclonal antisera or mock antisera were passively administered to rabbits before either intravenous infection with 10¹¹ CFU S. pneumoniae or corneal infection with 10⁵ CFU of S. pneumoniae. RESULTS After active immunization, clinical scores of corneas of the rabbits immunized with ψPLY and Freund's adjuvant were significantly lower than scores of the rabbits that were mock immunized with PBS and Freund's adjuvant or with PPSV23 and Freund's adjuvant at 48 hours after infection (P ≤ 0.0010), whereas rabbits immunized with PPSV23 and Freund's adjuvant failed to show differences in clinical scores compared with those in mock-immunized rabbits (P = 1.00) at 24 and 48 hours after infection. Antisera from rabbits actively immunized with PPSV23 and Freund's adjuvant were nonopsonizing. Bacterial loads recovered from infected corneas were higher for the ψPLY- and PPSV23-immunized rabbits after infection with WU2, when compared with the mock-immunized rabbits (P ≤ 0.007). Conversely, after infection with K1443, the ψPLY-immunized rabbits had lower bacterial loads than the control rabbits (P = 0.0008). Quantitation of IgG, IgA, and IgM in the sera of ψPLY-immunized rabbits showed high concentrations of PLY-specific IgG. Furthermore, anti-PLY IgG purified from ψPLY-immunized rabbits neutralized the cytolytic effects of PLY on human corneal epithelial cells. Passive administration of serotype-specific antisera capable of opsonizing and killing S. pneumoniae protected against pneumococcal bacteremia (P ≤ 0.05), but not against keratitis (P ≥ 0.476). CONCLUSIONS Active immunization with pneumococcal capsular polysaccharide and Freund's adjuvant fails to produce opsonizing antibodies, and passive administration of serotype specific opsonizing antibodies offers no protection against pneumococcal keratitis in the rabbit, whereas active immunization with the conserved protein virulence factor PLY and Freund's adjuvant is able to reduce corneal inflammation associated with pneumococcal keratitis, but has variable effects on bacterial loads in the cornea.