Characterization of Protective Mucosal and Systemic Immune Responses Elicited by Pneumococcal Surface Protein PspA and PspC Nasal Vaccines against a Respiratory Pneumococcal Challenge in Mice
Characterization of Protective Mucosal and Systemic Immune Responses Elicited by Pneumococcal Surface Protein PspA and PspC Nasal Vaccines against a Respiratory Pneumococcal Challenge in Mice
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DOI：
10.1128/cvi.00395-08
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发表时间：
2009-05-01
影响因子：
--
通讯作者：
Oliveira, M. L. S.
中科院分区：
文献类型：
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作者：
Ferreira, D. M.;Darrieux, M.;Oliveira, M. L. S.
肺炎球菌表面蛋白A（PspA）和PspC是参与肺炎链球菌粘附于上皮细胞和/或逃避免疫系统的毒力因子。在此，评价了由作为重组蛋白的两种抗原组成的粘膜疫苗或由干酪乳杆菌递送的粘膜疫苗诱导的免疫应答。没有一种PspC疫苗保护小鼠免受肺炎球菌菌株ATCC 6303的侵入性攻击。另一方面，用由来自进化枝5的PspA（PspA 5或L.表达PspA 5的干酪素）。保护性反应的特点是Th 1型高水平的免疫球蛋白G2 a的生产，有效的补体沉积，释放促炎细胞因子，和中性粒细胞浸润。用PspA 5鼻内免疫引起最高水平的保护，其特征在于分别通过肺和脾细胞增加白细胞介素-17和γ干扰素的分泌水平，以及呼吸道中低水平的肿瘤坏死因子α。
Pneumococcal surface protein A (PspA) and PspC are virulence factors that are involved in the adhesion of Streptococcus pneumoniae to epithelial cells and/or evasion from the immune system. Here, the immune responses induced by mucosal vaccines composed of both antigens as recombinant proteins or delivered by Lactobacillus casei were evaluated. None of the PspC vaccines protected mice against an invasive challenge with pneumococcal strain ATCC 6303. On the other hand, protection was observed for immunization with vaccines composed of PspA from clade 5 (PspA5 or L. casei expressing PspA5) through the intranasal route. The protective response was distinguished by a Th1 profile with high levels of immunoglobulin G2a production, efficient complement deposition, release of proinflammatory cytokines, and infiltration of neutrophils. Intranasal immunization with PspA5 elicited the highest level of protection, characterized by increased levels of secretion of interleukin-17 and gamma interferon by lung and spleen cells, respectively, and low levels of tumor necrosis factor alpha in the respiratory tract.