Journal
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
Volume 97, Issue 24, Pages 10445-10452Publisher
SPRINGER
DOI: 10.1007/s00253-013-5257-3
Keywords
Coxsackievirus A16; Vaccine; Virus-like particles; Saccharomyces cerevisiae
Categories
Funding
- Beijing Natural Science Foundation [7122129, 7112108]
- National Natural Science Foundation of China [81000721, 31270195]
- Beijing Nova Program of Science and Technology [2010B041]
- 100 Talents' Program of Chinese Academy of Sciences
- Shanghai PuJiang Career Development Award [09PJ1411400]
- 973 Project [2010CB912403]
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Hand, foot, and mouth disease (HFMD) has caused significant morbidity and mortality in the Asia-Pacific regions, particularly in infants and young children. Coxsackievirus A16 (CA16) represents one of the major causative agents for HFMD, and the development of a safe and effective vaccine preventing CA16 infections has become a public health priority. In this study, we have developed a yeast system for the production of virus-like particles (VLPs) for CA16 by co-expressing P1 and 3CD of CA16 in Saccharomyces cerevisiae. These VLPs exhibit similarity in both protein composition and morphology as empty particles from CA16-infected cells. Immunization with CA16 VLPs in mice potently induced CA16-specific IgG and neutralization antibodies in a dose-dependent manner. IgG subclass isotyping revealed that IgG1 and lgG2b were dominantly induced by VLPs. Meanwhile, cytokine profiling demonstrated that immunization with VLPs significantly induced the secretion of IFN-gamma, indicating potent cellular immune response. Furthermore, in vivo challenge experiments showed that passive immunization with anti-VLPs sera conferred full protection against lethal CA16 challenge in neonate mice. Taken together, our data demonstrated that VLPs produced in yeast might have the potential to be further developed as a vaccine candidate against HFMD.
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