BCHT has established 4 technology platforms regarding antigen preparation, final product and adjuvant technology, etc., laying a solid technical foundation for vaccine R&D and the industrialization.
These platforms are complementary to exert a strong synergistic effect, enabling more economical and efficient development of vaccine products and construction of vaccine portfolios. They do not only give support to continual upgrading of marketed vaccines, but also provide guarantee for successful marketing of new vaccines.
1.Virus culture scale-up technology platform
On the virus culture scale-up technology platform, virus culture on a large scale is realized in a suitable culture system, mainly including: cell factory or bioreactor for cell culture to prepare viral vaccines.
The virus culture scale-up technology platform is based on human diploid cell and Vero cell culture technologies. On this platform, with larger cell culture area per unit volume, high virus yield can be guaranteed; optimal cell and virus culture conditions have been defined through research. Good application cases of this platform include the marketed varicella and rabies vaccine (Vero cell), freeze-dried rabies vaccine (Vero cell) for human use and live attenuated herpes zoster vaccine which are under research.
2. Final product and adjuvant technology platform
Final product refers to drug products that are made in certain required dosage forms to be used for the target population to meet their needs of treatment or prevention. For vaccine products, which are biologically active, the main dosage forms are freeze-dried and liquid dosage forms; reasonable dosage forms can help achieving the efficacy and maintain the stability of vaccines.
An adjuvant is a non-specific immune enhancer which, when delivered together with an antigen or in advance into the body, can enhance the immune response of the body to the antigen or change the type of immune response. The commonly used adjuvants currently include aluminum adjuvant, MF59, etc. BCHT has gradually established a final product and adjuvant technology platform with years of efforts in design and characterization of new vaccine adjuvant systems and optimization of formulation process, compatibility evaluation between adjuvant systems and specific antigen candidates, optimization of combination of antigen and adjuvant systems, research on immunization strategies and evaluation of immune protective effects.
Benefiting from the deep research on protectants, BCHT has successfully developed the globally first varicella vaccine, live with a validity period of 36 months, and developed a liquid rabies vaccine with a prolonged validity period of 18 months (vs. traditional 12 months). For the influenza vaccine, live, nasal, freeze-dried, BCHT is developing a liquid dosage form in order to increase the convenience of administration. At present, clinical trial approval has been obtained for this product, and its formula of protectants has become internationally patented.
After nearly 3 years of exploration, a Nano-aluminum adjuvant has been developed. It has been applied in the diphtheria, tetanus and acellular pertussis combined vaccine for which a clinical approval has been obtained. The Nano-aluminum adjuvant will also be used in RSV and other vaccines. BCHT has developed the BK-01 adjuvant as well, which is already used in the development of split-virion influenza vaccine.
The establishment of the final product and adjuvant technology platform provides a basis for the marketing of other vaccines in the future.
3.Genetic engineering technology platform
Genetic engineering, theoretically based on molecular genetics and using modern molecular biological and microbiological methods, is the process of constructing recombinant DNA (rDNA) molecules in vitro with genetic materials from different sources and introducing these molecules into stromal cells or bacteria to obtain recombinant biological products.
The genetic engineering technology platform mainly includes technologies for nucleic acid vaccine preparation, expression of virus-like particles in E. coli system, expression of fully human monoclonal antibodies in CHO cells, baculovirus-insect cell expression system and other technologies. This platform has been applied to introduce optimized antigen genes into vectors, develop key technologies and construct an application platform for genetic engineering vaccine candidates, and construct, evaluate, and develop novel therapeutic and preventive genetically engineered, DNA, and viral vector vaccine candidates for major diseases such as malignant tumors, Alzheimer’s disease, tuberculosis, pneumonia, etc.
Relying on this technology platform, BCHT is developing RSV vaccine, tumor therapeutic vaccine, vaccine for Alzheimer’s disease, fully human anti-rabies virus monoclonal antibody, fully human anti-tetanus toxin monoclonal antibody and other preventive and therapeutic products. Among them, the tumor therapeutic vaccine has been designated as a National Science and Technology Major Project on New Drug Creation during the 12th Five-Year Plan Period.
4.Bacterial vaccine technology platform
Bacterial vaccine technology is used to develop bacterial vaccines and produce them on a large scale with extracted bacterial polysaccharides and toxins after large-scale bacterial culture in fermentation tanks. On the bacterial vaccine technology platform, polysaccharide protein conjugate vaccines as bacterial polysaccharide-protein carrier complexes to present enhanced immunogenicity are also possible by protein glycan coupling technology.
On this platform, purification schemes specific to the physicochemical properties of polysaccharides or toxins are designed, covering salting out, phenol extraction and alcohol precipitation, and chromatography processes; toxins are be detoxified by inactivators to obtain toxoids; large-scale bacterial fermentation and polysaccharide and protein purification technologies are all common core technologies for bacterial vaccines and genetically engineered vaccines that use bacteria as the production substrate. By virtue of this platform, BCHT is currently developing the diphtheria, tetanus and acellular pertussis combined vaccine, for which a clinical approval has been obtained, and haemophilus influenzae type b conjugate vaccine.