The monoglycosylated recombinant hemagglutinin protein vaccine and monoglycosylated influenza split virus vaccine are effective vaccines with cross-protection against H1N1 virus infections in mouse and ferret model

• Main Authors: Yung-Chieh Tseng, 曾勇傑
• Other Authors: Che Ma
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/09273145611452145495

博士 === 國防醫學院 === 生命科學研究所 === 105 === Each year influenza virus infections cause hundreds of thousands of deaths worldwide and a significant level of morbidity with great economic loss. Vaccination of the trivalent or quadrivalent inactivated virus vaccine produced from embryonated chicken eggs is at present the most prevalent method to prevent the infections. However, current influenza vaccines are only effective against closely matched circulating strains and must be updated and administered yearly. Therefore, generating a vaccine which can provide a broad protection is a major challenge for influenza vaccine development. In our hypothesis, the glycosylation on viral surface proteins acts as a shield which mask the conserved epitopes. In this study, we trimmed down the glycan on hemagglutinin which is the major antigen of influenza virus to a single N-acetylglucosamine at each N-glycosylation site (HAmg). The monoglycosylated recombinant HA vaccine can provide better cross-protection compared with the ordinary fully glycosylated HA (HAfg) in mice and ferret model. For adapted the concept of monoglycosylated vaccine into current industrial vaccine production, we produced monoglycosylated inactivated split H1N1 virus vaccine from chicken eggs by an N-glycosylation process inhibitor and an endo-glycosidase, and intramuscularly immunized mice to examine its efficacy. Compared to vaccination of the traditional influenza vaccine with complex glycosylation from eggs, the monoglycosylated split virus vaccine provided better protection against a lethal dose of virus challenges in mice. The enhanced antibody responses induced by the monoglycosylated vaccine immunization include higher neutralization activity, better hemagglutination inhibition, more hemagglutinin stem-specific antibodies and interestingly a higher antibody-dependent cellular cytotoxicity. This study provides a simple procedure to enhance the cross-strain protection of influenza vaccine by removing glycan shields from virus surface antigens through modifications of the current egg-based process that is suitable for industrial-scale production.