1. Effects of Size and Surface Properties of Nanodiamonds on the Immunogenicity of Plant-Based H5 Protein of A/H5N1 Virus in Mice
- Author
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Van Thi Pham, Ha Hoang Chu, Phuong Minh Thi Nguyen, Huan-Cheng Chang, Minh Pham, Tram Vi, Vy Thai Trinh, Ngoc Bich Pham, Huyen Thi Bui, Hsin-Hung Lin, Thao Bich Thi Le, Thuong Thi Ho, Chi Van Phan, Tra Thi Nguyen, and Wesley Wei-Wen Hsiao
- Subjects
Hemagglutination ,General Chemical Engineering ,nanodiamond ,02 engineering and technology ,Article ,03 medical and health sciences ,H5 protein ,Antigen ,In vivo ,size effect ,General Materials Science ,Nanodiamond ,avian influenza virus A/H5N1 ,QD1-999 ,030304 developmental biology ,0303 health sciences ,biology ,Chemistry ,Immunogenicity ,021001 nanoscience & nanotechnology ,In vitro ,Biophysics ,biology.protein ,surface properties ,Antibody ,0210 nano-technology ,Conjugate - Abstract
Nanodiamond (ND) has recently emerged as a potential nanomaterial for nanovaccine development. Here, a plant-based haemagglutinin protein (H5.c2) of A/H5N1 virus was conjugated with detonation NDs (DND) of 3.7 nm in diameter (ND4), and high-pressure and high-temperature (HPHT) oxidative NDs of ~40–70 nm (ND40) and ~100–250 nm (ND100) in diameter. Our results revealed that the surface charge, but not the size of NDs, is crucial to the protein conjugation, as well as the in vitro and in vivo behaviors of H5.c2:ND conjugates. Positively charged ND4 does not effectively form stable conjugates with H5.c2, and has no impact on the immunogenicity of the protein both in vitro and in vivo. In contrast, the negatively oxidized NDs (ND40 and ND100) are excellent protein antigen carriers. When compared to free H5.c2, H5.c2:ND40, and H5.c2:ND100 conjugates are highly immunogenic with hemagglutination titers that are both 16 times higher than that of the free H5.c2 protein. Notably, H5.c2:ND40 and H5.c2:ND100 conjugates induce over 3-folds stronger production of both H5.c2-specific-IgG and neutralizing antibodies against A/H5N1 than free H5.c2 in mice. These findings support the innovative strategy of using negatively oxidized ND particles as novel antigen carriers for vaccine development, while also highlighting the importance of particle characterization before use.
- Published
- 2021
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