Vaccine was one of the two core pillar when NIDVD set up, and now, innovative vaccine is one of the most important directions leading us to sustainable development. In its inception, NIDVD has conducted a systematic research on vaccines, and made a series of research results. With the continuous development, the vaccine research, especially the innovative vaccine, become a higher platform, which further enrich the research systems of innovative vaccines and product line.
1. Technology platform of innovative vaccine
Before the establishment of NIDVD, genetic engineering design of vaccine was mainly based on the amino acid primary structure of antigens, and made outstanding achievements in the development of Hepatitis E prophylactic vaccine and the first generation HPV prophylactic vaccine. Since the establishment of NIDVD, with the rapid development of structural biology and virology, the research and development technology of innovative vaccine were expanded, in which three-dimensional structure determination platform of biological macromolecular played a fundamental supporting role. Structural basis of most antigen epitopes in virus have been clarified with the application of X-ray crystallography platform, Cryo-electronic microscope platform and bioinformatics platform, laying a solid foundation for molecular design and development of innovative vaccine.
2. Achievements of innovative vaccine
By utilizing innovational vaccine research platform, we have developed five recombinant human vaccines and acquired many representative results, especially in the research of such many infectious viruses as HPV, HEV, HBV, VZV and so on.
In the research and development of Human HEV vaccine, we revealed the structural basis of HEV VLPs by X-ray crystallography investigation of the structure of HEV capsid protein and immune complex formed with its functional antibodies (PNAS 2011; PLoS Patho 2009, Vaccine 2005). And finally designed the HEV VLPs vaccine. Further, we confirmed the safety and long-term efficacy of the recombinant Human HEV vaccine. These results had been published in academic journals such as Lancet, PNAS and so on. After 14-years research and exploration, the vaccine was first approved for human usage worldwide and successfully launched onto the market of China on Oct 27th, 2012, which earned us the acclaim of the entire scientific community (Nature 2012,491, 21-22, etc.). The HEV vaccine provides effective and initiative tool for human to prevent HEV infection. It turned out to be a feasible access to develop VLP vaccine by prokaryotic expression platform, which had changed the traditional cognition in the field of developing vaccine at home and abroad. According to these achievements, we have applied 12 patents in 14 countries and acquired award for Chinese outstanding patented invention in 2012.
For human papillomavirus vaccine, we firstly successfully accomplished the production of HPV VLPs through E.coli expression systems in middle stage test workshop by developing an original technology in expression and purification. Up to now, we have applied for 31 patents including 13 international patents, and one of 15 patents have authorized, containing 6 international patents. The primary advantages of HPV vaccine production systems established by NIDVD including simple technology, ease of scale-up, low-cost and possessing proprietary intellectual property rights. By now, the bivalent HPV 16/18 vaccine for preventing cervical cancer has been completed III phase clinical trial, which is predicted to come into market in 2018. Meanwhile the II phase clinical trial of bivalent HPV 6/11 vaccine for preventing verruca acuminate is carrying on. And the application of two-generation of nine-valent HPV vaccine for clinical trial has been accepted. Nowadays, the third-generation of HPV vaccine based on our structural vaccinology platform is progressing successfully, which will push our country’s HPV vaccine research to be a leading position around the world.
Progress on HBV therapeutic vaccine: SEQ13，a potential dominant epitope for HBV therapeutic vaccine, was obtained by the screening of HBV neutralizing antibody. Based on the virus-like particle display platform and recognizing targets of the potential therapeutic antibody E6F6，we completed the construction of virus-like particle to display the candidate epitopes, used HBC149 as display vector and HBV transgenic mice as evaluation models， SEQ13 was selected from 23 kinds of HBsAg epitopes peptides in hydrophilic region and had therapeutic effect on HBV immune tolerance mice. As a candidate for HBV therapeutic vaccine, SEQ13 vaccine had obtained proprietary intellectual property rights and have accomplished comprehensive laboratory evaluation of pharmacology and drug efficacy, which lay the foundation for transformation into downstream products, was expected to offer a new treatment for chronic HBV infection.
3. Achievements transformation of Innovative vaccine
Five innovative vaccines developed by NIDVD were all completed industrial transformation by Beijing Wantai Bio-Pharmaceutical Co., Ltd. and Xiamen Innovax Biotech Co., Ltd, resulting in significant economic benefits. Since Hepatitis E vaccine Hecolin® came to market, total sales were more than 600,000, the output value was over RMB 30 million. After that, Hepatitis E vaccine have been provided important technical support for the prevention and control of Hepatitis E diseases. Furthermore, the bivalent HPV 16/18 recombinant vaccine will be in market around 2018, its annual sales expected will be more than 1 billion.
4. Influence of NIDVD in innovative vaccine area
NIDVD is a national leading lab in the research area of innovative vaccine. In 2013, School of Public Health in Xiamen University as a core team to established "State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics" and then approved by the Ministry of science and technology of China. In future, NIDVD will take advantages of different national center platform to further make more contributions and enhance its influence within the field of innovative vaccine.