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Original Articles

Enterovirus D68 virus-like particles expressed in Pichia pastoris potently induce neutralizing antibody responses and confer protection against lethal viral infection in mice

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Pages 1-22 | Received 02 Aug 2017, Accepted 12 Nov 2017, Published online: 10 Jan 2018
 

Abstract

Enterovirus D68 (EV-D68) has been increasingly associated with severe respiratory illness and neurological complications in children worldwide. However, no vaccine is currently available to prevent EV-D68 infection. In the present study, we investigated the possibility of developing a virus-like particle (VLP)-based EV-D68 vaccine. We found that co-expression of the P1 precursor and 3CD protease of EV-D68 in Pichia pastoris yeast resulted in the generation of EV-D68 VLPs, which were composed of processed VP0, VP1, and VP3 capsid proteins and were visualized as ~30 nm spherical particles. Mice immunized with these VLPs produced serum antibodies capable of specifically neutralizing EV-D68 infections in vitro. The in vivo protective efficacy of the EV-D68 VLP candidate vaccine was assessed in two challenge experiments. The first challenge experiment showed that neonatal mice born to the VLP-immunized dams were fully protected from lethal EV-D68 infection, whereas in the second experiment, passive transfer of anti-VLP sera was found to confer complete protection in the recipient mice. Collectively, these results demonstrate the proof-of-concept for VLP-based broadly effective EV-D68 vaccines.

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (31370930) and the Science and Technology Commission of Shanghai Municipality (15XD1524900) the TOTAL Foundation, the Youth Innovation Promotion Association of CAS (2016249), and National Natural Science Foundation ofChina (31500153). C.Z. was partially supported by a postdoc fellowship from the Guangzhou Women and Children’s Medical Center. We acknowledge the China National Center for Protein Sciences (Shanghai) for providing electron microscopy resources.