Nasal vaccination with pneumococcal surface protein A in combination with cationic liposomes consisting of DOTAP and DC-chol confers antigen-mediated protective immunity against Streptococcus pneumoniae infections in mice
Nasal vaccination with pneumococcal surface protein A in combination with cationic liposomes consisting of DOTAP and DC-chol confers antigen-mediated protective immunity against Streptococcus pneumoniae infections in mice
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DOI：
10.1016/j.intimp.2018.06.027
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发表时间：
2018-08-01
影响因子：
5.6
通讯作者：
Aramaki, Yukihiko
中科院分区：
文献类型：
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作者：
Tada, Rui;Suzuki, Hidehiko;Aramaki, Yukihiko
传染病是全世界第二大死亡原因，这表明仍然需要制定有效防治病原体的新的和改进的战略。肺炎链球菌是引起肺炎的致病性最强的细菌，死亡率高，尤其是儿童和老年人。由于S.肺炎链球菌感染，采用非依赖型的粘膜疫苗将是预防和治疗肺炎链球菌引起的疾病的最佳途径。肺炎。本研究以肺炎球菌表面蛋白A（PspA）和1，2-二油酰基-3-三甲基铵丙烷（DOTAP）及胆固醇313-N（二甲氨基乙基氨基甲酸酯（DC-chol））组成的阳离子脂质体（DOTAP/DC-chol脂质体）为载体，制备了肺炎球菌鼻用疫苗。在S.肺炎感染。鼻内接种PspA和DOTAP/DC-chol脂质体可产生针对致死性吸入S.提高感染小鼠的存活率。此外，鼻内免疫PspA和DOTAP/ DC-chol脂质体不仅诱导粘膜和全身区室产生PspA特异性伊加和IgG，而且还引起PspA特异性Th 17应答，其在控制S.通过宿主先天免疫应答感染肺炎。我们进一步证明DOTAP/DC-chol脂质体增强鼻树突状细胞（DC）对PspA的摄取，这可能是诱导对S.肺炎感染。这些结果表明，DOTAP/DC-chol脂质体将是一种有效的粘膜疫苗系统，用于针对肺炎球菌感染的不依赖于菌型的通用鼻疫苗。
Infectious diseases are the second leading cause of death worldwide, suggesting that there is still a need for the development of new and improved strategies for combating pathogens effectively. Streptococcus pneumoniae is the most virulent bacteria causing pneumonia with high mortality, especially in children and the elderly. Because of the emergence of antibiotic resistance in S. pneumoniae, employing a serotype-independent mucosal vaccine would be the best approach to prevent and treat the diseases caused by S. pneumoniae. In this study, we have developed a pneumococcal nasal vaccine, consisting of pneumococcal surface protein A (PspA) and cationic liposomes composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and cholesteryl 313-N(dimethylaminoethypcarbamate (DC-chol) (DOTAP/DC-chol liposome). The efficiency of this cationic liposomebased PspA nasal vaccine was examined in a murine model of S. pneumoniae infection. Intranasal vaccination with PspA and DOTAP/DC-chol liposomes conferred protective immunity against lethal inhalation of S. pneumoniae, improving the survival rate of infected mice. Moreover, intranasal immunization with PspA and DOTAP/ DC-chol liposomes not only induced the production of PspA-specific IgA and IgG by both mucosal and systemic compartments but also elicited PspA-specific Th17 responses, which play a pivotal role in controlling S. pneumoniae infection by host innate immune response. We further demonstrated that DOTAP/DC-chol liposomes enhanced PspA uptake by nasal dendritic cells (DCs), which might be a mechanism for the induction of protective immune responses to S. pneumoniae infection. These results show that DOTAP/DC-chol liposome would be an efficient mucosal vaccine system for a serotype-independent universal nasal vaccine against pneumococcal infection.