A systems approach to designing next generation vaccines: combining α-galactose modified antigens with nanoparticle platforms.

A systems approach to designing next generation vaccines: combining α-galactose modified antigens with nanoparticle platforms.
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DOI:
10.1038/srep03775
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发表时间:
2014-01-20
期刊:
影响因子:
4.6
通讯作者:
Wannemuehler MJ
Wannemuehler MJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Phanse Y;Carrillo-Conde BR;Ramer-Tait AE;Broderick S;Kong CS;Rajan K;Flick R;Mandell RB;Narasimhan B;Wannemuehler MJ

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需要创新的疫苗平台来制定针对新出现和再出现疾病的有效对策。这些平台应直接抗原内化抗原呈递细胞和促进免疫原性反应。本文提出了一种结合α半乳糖(αGal)修饰抗原和两亲性聚酸酐纳米颗粒作为疫苗递送载体的创新系统方法,以合理设计疫苗配方。由可溶性α gal修饰抗原和纳米颗粒包封的未修饰抗原组成的方案诱导了高滴度、高亲和力的抗体反应,抗原肽的表位识别范围比其他方案更广。与传统佐剂相比,抗原特异性CD4+ T细胞的增殖也得到了增强。将技术平台和增强免疫反应研究与肽阵列和信息学分析相结合,为针对新出现和再出现的病原体的下一代疫苗平台的合理、基于系统的设计提供了新的范例。
Innovative vaccine platforms are needed to develop effective countermeasures against emerging and re-emerging diseases. These platforms should direct antigen internalization by antigen presenting cells and promote immunogenic responses. This work describes an innovative systems approach combining two novel platforms, αGalactose (αGal)-modification of antigens and amphiphilic polyanhydride nanoparticles as vaccine delivery vehicles, to rationally design vaccine formulations. Regimens comprising soluble αGal-modified antigen and nanoparticle-encapsulated unmodified antigen induced a high titer, high avidity antibody response with broader epitope recognition of antigenic peptides than other regimen. Proliferation of antigen-specific CD4+ T cells was also enhanced compared to a traditional adjuvant. Combining the technology platforms and augmenting immune response studies with peptide arrays and informatics analysis provides a new paradigm for rational, systems-based design of next generation vaccine platforms against emerging and re-emerging pathogens.
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