Yamamoto M, Briles D E, Yamamoto S, Ohmura M, Kiyono H, McGhee J R
Department of Oral Biology, University of Alabama Medical Center, Birmingham 35294, USA.
J Immunol. 1998 Oct 15;161(8):4115-21.
In this study, we demonstrated that pneumococcal surface protein A (PspA) nasally administered with a nontoxic A subunit mutant of cholera toxin (mCT) S61F elicited a protective immune response. Immunization with PspA and mCT elicited higher levels of PspA-specific IgG and IgA Abs in serum and of IgG and IgA anti-PspA Ab-forming cells in spleens, cervical lymph nodes (CLN), and lung tissue when compared to nonimmunized mice. Furthermore, significant PspA-specific IgA Abs were induced in saliva and nasal secretions. These responses were dependent on the use of mCT as a mucosal adjuvant. The PspA-specific Ab responses induced by mCT S61F were comparable with those induced by native CT (nCT). Analysis of cytokine responses showed that nasal PspA plus mCT S61F enhanced the induction of PspA-specific CD4+ T cells producing IL-4 but not IFN-gamma in CLN at both the protein and mRNA levels. Importantly, significant numbers of mice intranasally immunized with PspA plus mCT S61F were protected from lethal challenge with capsular serotype 3 Streptococcus pneumoniae A66. These results show that intranasal administration of PspA together with mCT S61F is an effective mucosal vaccine against pneumococcal infection and induces CD4+ Th2-type cells, which provide help for both mucosal and systemic Ab responses.
在本研究中，我们证明，将肺炎球菌表面蛋白A（PspA）与霍乱毒素（CT）无毒A亚基突变体S61F经鼻给药可引发保护性免疫反应。与未免疫的小鼠相比，用PspA和mCT免疫可使血清中PspA特异性IgG和IgA抗体以及脾脏、颈部淋巴结（CLN）和肺组织中IgG和IgA抗PspA抗体形成细胞的水平更高。此外，在唾液和鼻分泌物中诱导出了显著的PspA特异性IgA抗体。这些反应依赖于使用mCT作为黏膜佐剂。mCT S61F诱导的PspA特异性抗体反应与天然CT（nCT）诱导的反应相当。细胞因子反应分析表明，经鼻给予PspA加mCT S61F在蛋白质和mRNA水平上均增强了CLN中产生IL-4而非IFN-γ的PspA特异性CD4+ T细胞的诱导。重要的是，大量经鼻用PspA加mCT S61F免疫的小鼠对3型荚膜肺炎链球菌A66的致死性攻击具有抵抗力。这些结果表明，经鼻给予PspA与mCT S61F一起是一种针对肺炎球菌感染的有效黏膜疫苗，并诱导CD4+ Th2型细胞，其为黏膜和全身抗体反应提供帮助。
