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23 September 2016 : Animal Research  

Virus-Like Particles Produced in Pichia Pastoris Induce Protective Immune Responses Against Coxsackievirus A16 in Mice

Qianjin FengABCD, Yaqing HeABCDEFG, Jiahai LuABCDEFG

DOI: 10.12659/MSM.900380

Med Sci Monit 2016; 22:3370-3382

Abstract

BACKGROUND: Coxsackievirus A16 (CA16) is one of the main causative agents of hand, foot, and mouth disease (HFMD), and the development of a safe and effective vaccine has been a top priority among CA16 researchers.

MATERIAL AND METHODS: In this study, we developed a Pichia pastoris yeast system for secretory expression of the virus-like particles (VLPs) for CA16 by co-expression of the P1 and 3CD proteins of CA16. SDS-PAGE, Western blot, and transmission electron microscopy (TEM) were performed to identify the formation of VLPs. Immunogenicity and vaccine efficacy of the CA16 VLPs were assessed in BABL/c mouse models.

RESULTS: Biochemical and biophysical analysis showed that the yeast-expressed CA16 VLPs were composed of VP0, VP1, and VP3 capsid subunit proteins, and present spherical particles with a diameter of 30 nm, similar to the parental infectious CA16 virus. Furthermore, CA16 VLPs elicited potent humoral and cellular immune responses, and VLPs-immunized sera conferred efficient protection to neonatal mice against lethal CA16 challenge.

CONCLUSIONS: Our results demonstrate that VLPs produced in Pichia pastoris represent a safe and effective vaccine strategy for CA16.

Keywords: Coxsackievirus Infections, Immunogenetics, Pichia, Vaccines, Virus-Like Particle

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750