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Nanomedicine. 2019 Apr;17:223-235. doi: 10.1016/j.nano.2019.01.012. Epub 2019 Jan 26.

Attachment of flagellin enhances the immunostimulatory activity of a hemagglutinin-ferritin nano-cage.

Author information

1
Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
2
Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon, Republic of Korea.
3
Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon, Republic of Korea; Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.
4
Institute of Biotechnology, Chungnam National University, Daejeon, Republic of Korea. Electronic address: hlee@cnu.ac.kr.
5
Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. Electronic address: jieoh@kaist.ac.kr.

Abstract

Hemagglutinin (HA) displayed on a ferritin nano-cage has been shown to be effective in generating a potent immune response against a broad range of influenza infections. Here, we showed that conjugation of flagellin together with HA to the exterior surface of the ferritin cage greatly enhanced not only the humoral immune response in mice but also antigen-specific T cell responses that include Th1 cytokine secretion. The effect of flagellin remained essentially unchanged when the molar ratio of flagellin to HA was reduced from 1:1 to 1:3. Injection of the ferritin-HA-flagellin cage provided protection against lethal virus challenge in mice. We used a small immunoglobulin fragment VL12.3 as a convenient method for attaching HA and flagellin to the ferritin cage. This attachment method can be used for rapid screening of a variety of protein cages and nano-assemblies to identify the most suitable carrier and adjuvant proteins for the target antigen.

KEYWORDS:

Conjugation; Ferritin; Flagellin; Hemagglutinin; Influenza; Nanoparticles

PMID:
30695729
DOI:
10.1016/j.nano.2019.01.012

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