Intranasal vaccination of neonatal mice with polysaccharide conjugate vaccine for protection against pneumococcal otitis media.
Intranasal vaccination of neonatal mice with polysaccharide conjugate vaccine for protection against pneumococcal otitis media.
复制标题
用多糖结合疫苗对新生小鼠进行鼻内接种，以预防肺炎球菌中耳炎。
DOI：
10.1016/j.vaccine.2006.04.033
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Metzger,DennisW
中科院分区：
文献类型：
--
作者：
Sabirov,Albert;Metzger,DennisW
肺炎链球菌是幼儿急性中耳炎(OM)的主要细菌病因，经常会产生侵袭性疾病。典型的肌肉内接种途径对OM的预防效果不佳。在本研究中，我们鼻腔(I.N.)以IL-12为黏膜佐剂，给新生1周龄小鼠接种肺炎链球菌多糖结合疫苗。通过用细菌攻击免疫的婴儿(3周大)小鼠，诱发OM和侵袭性疾病，测试了这种治疗的保护效果。I.N.接种疫苗可以提高野生型(但不是干扰素-γ−/−)小鼠中耳冲洗液和血清中的特异性抗体水平。在IL-12存在的情况下进行免疫，可增强肺炎链球菌从ME中的清除。用免疫小鼠的ME洗涤液或血清对细菌进行调理，可增加幼稚小鼠ME的细菌清除率。此外，在OM诱导的侵袭性肺炎球菌感染后，免疫小鼠的存活率为89%，而未接种疫苗的小鼠存活率为22%。这些结果表明，I.N.在IL-12存在的情况下接种新生小鼠能够增强依赖干扰素-γ的ME黏膜和系统对肺炎球菌的免疫应答，并有效地预防OM和侵袭性感染。
Streptococcus pneumoniae is the leading bacterial cause of acute otitis media (OM) in young children, and can often produce invasive disease. Typical intramuscular routes of vaccination are poorly protective against development of OM. In the present study, we intranasally (i.n.) inoculated neonatal 1-week-old mice with pneumococcal polysaccharide conjugate vaccine using IL-12 as a mucosal adjuvant. The protective efficacy of this treatment was tested by challenging immunized infant (3-week-old) mice with bacteria to induce OM and invasive disease. i.n. vaccination was found to enhance levels of specific antibodies in middle ear (ME) washes and sera from wild-type (but not IFN-γ−/−) mice. Immunization in the presence of IL-12 resulted in enhanced clearance of S. pneumoniae from the ME. Opsonization of bacteria with ME wash fluids or sera from immunized mice caused increased bacterial clearance from the ME of naïve mice. In addition, immunized mice demonstrated 89% survival after OM-induced invasive pneumococcal infection, compared to 22% survival in unvaccinated mice. These results indicate that i.n. vaccination of neonatal mice in the presence of IL-12 is able to enhance IFN-γ dependent ME mucosal and systemic immune responses to pneumococci and efficiently protect against both OM and invasive infection.