Development of Self-Assembled Protein Nanocage Spatially Functionalized with HA Stalk as a Broadly Cross-Reactive Influenza Vaccine Platform.
Development of Self-Assembled Protein Nanocage Spatially Functionalized with HA Stalk as a Broadly Cross-Reactive Influenza Vaccine Platform.
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DOI：
10.1021/acsnano.3c07669
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发表时间：
2023-12-26
期刊：
影响因子：
17.1
通讯作者：
Champion, Julie A.
中科院分区：
文献类型：
--
作者：
Park, Jaeyoung;Champion, Julie A.
关键词：
由于目前的季节性流感疫苗对错配、突变或大流行性流感病毒的保护作用有限，因此仍然需要开发通用流感疫苗。开发有效的通用流感疫苗的理想方法是将高度保守的抗原掺入多价支架中，以增强其免疫原性。在这里，我们开发了一种广泛交叉反应的流感疫苗，通过功能化自组装蛋白纳米笼（SAPN），其外表面有多个血凝素茎拷贝，内表面有基质蛋白2胞外域。 SAPN 是通过工程短卷绕线圈生成的，并通过 MD GROMACS 模拟设计。由于序列短，在免疫小鼠中没有观察到针对空 SAPN 支架的脱靶免疫反应。使用多价 SAPN 进行疫苗接种只会诱导高水平的仅与外部抗原发生广泛交叉反应的抗体，这证明了对设计的抗原放置的严格空间控制。这项工作展示了 SAPN 作为潜在流感疫苗的用途。
There remains a need for the development of a universal influenza vaccine, as current seasonal influenza vaccines exhibit limited protection against mismatched, mutated, or pandemic influenza viruses. A desirable approach to developing an effective universal influenza vaccine is the incorporation of highly conserved antigens in a multivalent scaffold that enhances their immunogenicity. Here, we develop a broadly cross-reactive influenza vaccine by functionalizing self-assembled protein nanocages (SAPNs) with multiple copies of the hemagglutinin stalk on the outer surface and matrix protein 2 ectodomain on the inner surface. SAPNs were generated by engineering short coiled coils, and the design was simulated by MD GROMACS. Due to the short sequences, off-target immune responses against empty SAPN scaffolds were not seen in immunized mice. Vaccination with the multivalent SAPNs induces high levels of broadly cross-reactive antibodies of only external antigens, demonstrating tight spatial control over the designed antigen placement. This work demonstrates the use of SAPNs as a potential influenza vaccine.
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