CD4 T Cell Memory and Antibody Responses Directed against the Pneumococcal Histidine Triad Proteins PhtD and PhtE following Nasopharyngeal Colonization and Immunization and Their Role in Protection against Pneumococcal Colonization in Mice
CD4 T Cell Memory and Antibody Responses Directed against the Pneumococcal Histidine Triad Proteins PhtD and PhtE following Nasopharyngeal Colonization and Immunization and Their Role in Protection against Pneumococcal Colonization in Mice
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DOI：
10.1128/iai.00313-13
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发表时间：
2013-10-01
影响因子：
3.1
通讯作者：
Pichichero, M. E.
中科院分区：
文献类型：
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作者：
Khan, M. N.;Pichichero, M. E.
本研究旨在了解候选疫苗PhtD和PhtE在肺炎球菌鼻咽（NP）定植中的作用，它们诱导CD 4 T细胞记忆和抗体应答的能力，以及它们对小鼠继发性肺炎球菌定植的保护作用。该研究还旨在了解用PhtD和PhtE免疫在小鼠中引发定性CD 4 T细胞记忆应答和保护免受肺炎球菌NP定植的潜力。构建了TIGR 4背景中的PhtD和PhtE同基因突变体（TIGR 4 Delta PhtD和TIGR 4 Delta PhtE），并且发现与用野生型TIGR 4定殖的小鼠相比，在小鼠鼻咽中随时间推移定殖密度显著降低。具有野生型TIGR 4、TIGR 4 Delta PhtD或TIGR 4 Delta PhtE的初次定殖的小鼠被保护免受野生型TIGR 4的二次定殖;然而，与具有野生型TIGR 4的初次定殖的小鼠相比，具有TIGR 4 Delta PhtD或TIGR 4 Delta PhtE的初次定殖的小鼠中二次定殖的清除更慢。发现定殖是PhtD和PhtE抗原的免疫事件（抗体应答）;然而，我们未能在任何定殖小鼠组中检测到任何抗原（PhtD或PhtE）特异性CD 4 T细胞应答。鼻内免疫PhtD或PhtE蛋白产生强大的血清抗体和CD 4 Th 1偏置的免疫记忆，并赋予对小鼠肺炎球菌定植的保护。我们得出结论，PhtD和PhtE显示出作为下一代肺炎球菌疫苗制剂组分的前景。
The present study was undertaken to understand the role of vaccine candidates PhtD and PhtE in pneumococcal nasopharyngeal (NP) colonization, their ability to induce CD4 T cell memory and antibody responses following primary NP colonization, and their contribution to protection against secondary pneumococcal colonization in mice. The study was also aimed at understanding the potential of immunization with PhtD and PhtE in eliciting qualitative CD4 T cell memory responses and protection against pneumococcal NP colonization in mice. PhtD and PhtE isogenic mutants in a TIGR4 background (TIGR4 Delta PhtD and TIGR4 Delta PhtE) were constructed and found to have a significantly reduced colonization density over time in the nasopharynges of mice compared to those of mice colonized with wild-type TIGR4. Mice with primary colonization by wild-type TIGR4, TIGR4 Delta PhtD, or TIGR4 Delta PhtE were protected against secondary colonization by wild-type TIGR4; nonetheless, the clearance of secondary colonization was slower in mice with primary colonization by either TIGR4 Delta PhtD or TIGR4 Delta PhtE than in mice with primary colonization by wild-type TIGR4. Colonization was found to be an immunizing event for PhtD and PhtE antigens (antibody response); however, we failed to detect any antigen (PhtD or PhtE)-specific CD4 T cell responses in any of the colonized groups of mice. Intranasal immunization with either PhtD or PhtE protein generated robust serum antibody and CD4 Th1-biased immune memory and conferred protection against pneumococcal colonization in mice. We conclude that PhtD and PhtE show promise as components in next-generation pneumococcal vaccine formulations.