Intranasal Vaccination with Chitosan-DNA Nanoparticles Expressing Pneumococcal Surface Antigen A Protects Mice against Nasopharyngeal Colonization by Streptococcus pneumoniae
Intranasal Vaccination with Chitosan-DNA Nanoparticles Expressing Pneumococcal Surface Antigen A Protects Mice against Nasopharyngeal Colonization by Streptococcus pneumoniae
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鼻内接种表达肺炎球菌表面抗原 A 的壳聚糖 DNA 纳米颗粒可保护小鼠免受肺炎链球菌在鼻咽部的定植
DOI：
10.1128/cvi.00263-10
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发表时间：
2011-01-01
影响因子：
--
通讯作者：
Fan, Xiaoyong
中科院分区：
文献类型：
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作者：
Xu, Jianghong;Dai, Wenjia;Fan, Xiaoyong
摘要肺炎链球菌是一种呼吸道致病菌，黏膜免疫应答在抵抗肺炎链球菌感染中起着重要作用。因此，鼻内接种可能是当前免疫策略的替代方法，并且有效的粘膜生物体递送系统是必要的。在这项研究中，用表达肺炎球菌表面抗原A（PsaA）的壳聚糖-DNA纳米颗粒鼻内免疫BALB/c小鼠。与裸DNA或chitosan-pVAX 1免疫小鼠相比，chitosan-psaA免疫小鼠血清中抗PsaA IgG抗体和粘膜灌洗液中抗IgA抗体水平显著升高。结果表明，壳聚糖-psaA免疫小鼠后，血清中IgG 1/IgG 2a抗体比例平衡，脾淋巴细胞中γ-干扰素（IFN-γ）和IL-17 A水平升高，粘膜洗涤液中IL-17 A水平升高，表明壳聚糖-psaA免疫小鼠后可诱导细胞免疫应答。此外，在用ATCC 6303（血清型3）鼻内攻击后，从用壳聚糖-psaA免疫的小鼠的鼻咽中回收的肺炎球菌显著少于对照组。这些结果表明，用壳聚糖-psaA粘膜免疫可以成功地产生粘膜和全身免疫应答，并防止肺炎球菌鼻咽定殖。因此，可以开发一种在鼻内给药后表达肺炎球菌主要免疫显性抗原的壳聚糖-DNA纳米颗粒疫苗来预防肺炎球菌感染。
ABSTRACT Streptococcus pneumoniae is a respiratory pathogen, and mucosal immune response plays a significant role in the defense against pneumococcal infections. Thus, intranasal vaccination may be an alternative approach to current immunization strategies, and effective delivery systems to mucosal organism are necessary. In this study, BALB/c mice were immunized intranasally with chitosan-DNA nanoparticles expressing pneumococcal surface antigen A (PsaA). Compared to levels in mice immunized with naked DNA or chitosan-pVAX1, anti-PsaA IgG antibody in serum and anti-IgA antibody in mucosal lavages were elevated significantly in mice immunized with chitosan-psaA. The balanced IgG1/IgG2a antibody ratio in serum, enhanced gamma interferon (IFN-γ) and IL-17A levels in spleen lymphocytes, and mucosal washes of mice immunized with chitosan-psaA suggested that cellular immune responses were induced. Furthermore, significantly fewer pneumococci were recovered from the nasopharynx of mice immunized with chitosan-psaA than for the control group following intranasal challenge with ATCC 6303 (serotype 3). These results demonstrated that mucosal immunization with chitosan-psaA may successfully generate mucosal and systemic immune responses and prevent pneumococcal nasopharyngeal colonization. Hence, a chitosan-DNA nanoparticle vaccine expressing pneumococcal major immunodominant antigens after intranasal administration could be developed to prevent pneumococcal infections.