Coxsackievirus A16-like particles produced in Pichia pastoris elicit high-titer neutralizing antibodies and confer protection against lethal viral challenge in mice

Antiviral Research
Chao ZhangZhong Huang

Abstract

Coxsackievirus A16 (CA16) is a major causative agent of hand, foot and mouse disease (HFMD) which has been affecting millions of young children annually in the Asia-Pacific region over the last seven years. However, no commercial CA16 vaccines are currently available. In the present study, we investigated the expression of virus-like particles (VLPs) of CA16 in Pichia pastoris yeast and their immunogenicity and protective efficacy in mice. We found that CA16-VLPs could be produced at relatively high levels in P. pastoris yeast transformed with a construct co-expressing the P1 and 3CD proteins of CA16. Mice immunized with the yeast-derived CA16-VLPs produced high-titer serum antibodies with potent neutralization effect specifically on CA16. More importantly, passive immunization with the yeast-derived VLPs fully protected neonatal mice against CA16 lethal challenge in both antisera transfer and maternal immunization experiments. Collectively, our results demonstrate that P. pastoris-derived CA16-VLPs represent a promising CA16 vaccine candidate with proven preclinical efficacy and desirable traits for manufacturing at industrial scale.

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Citations

Feb 8, 2018·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·Susanna Esposito, Nicola Principi
Jan 23, 2019·FEMS Yeast Research·Ravinder Kumar, Piyush Kumar
May 26, 2017·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Yuwei WengYansheng Yan
Sep 24, 2016·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Qianjin FengJiahai Lu
Jun 5, 2021·Applied Microbiology and Biotechnology·R Sahaya GlingstonShirisha Nagotu
Aug 13, 2021·Expert Opinion on Drug Discovery·Chih-Yeu Fang, Chia-Chyi Liu

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