The National Engineering Laboratory of AIDS Vaccine has carried out a lot of research work in the field of basic research and applied research of AIDS vaccine, which not only has innovation, but also pays attention to the transformation of these achievements, and has achieved economic and social benefits and achieved a series of excellent research results:
1. Based on the systematic epidemiological investigation in China, an HIV- 1 vaccine was designed for the epidemic strains of AIDS in China, which is different from the vaccine design scheme that has been carried out in international clinical research. GagPol and Env structural genes were constructed together in DNA vaccine and MVA, and they were modified. Vaccine target antigens include almost all HIV- 1 structural proteins, and these target antigens are efficiently expressed in cells of the body to form virus-like particles, which can induce cellular immunity and humoral immunity at the same time, and improve the vaccine protection effect to a greater extent; The combination of DNA vaccine and MVA virus vector vaccine greatly improves the intensity of specific immune response against HIV. In 2006, the vaccine took the lead in completing phase I clinical research and achieved the expected results. Phase I clinical trials show that there is no serious adverse reaction, and at the same time, it can produce a strong specific immune response against HIV- 1 in human body. The second phase clinical study of the vaccine began in March 2009. The results of the first phase show that the vaccine has good safety.
2. In the pathogenesis of HIV- 1 and the design of new anti-AIDS drugs, the mechanism of HIV escaping from the host defense system was explained for the first time. The research results were published in the international authoritative magazine Science in June 2003, and the paper has been cited for 359 times. Further research work is published in J.Virol, Gene &; Development magazine. This discovery has attracted the attention of scientists in the field of AIDS prevention and treatment all over the world, which provides a theoretical basis for studying the mechanism of AIDS escaping antiviral factors in vivo and fills the gap in the basic theoretical research of AIDS. At present, our laboratory is designing and developing small molecular inhibitors according to this goal, and has made some progress.
3. Established the technical platform for the design, development and production of DNA vaccine and virus vector vaccine and the technical platform for the quality control of AIDS vaccine, and took the lead in establishing the quality control standard of AIDS vaccine in China.
4. Familiar with the design, preparation and characterization methods of liposomes with different properties in the research of protein peptides and liposome vaccines.
5. In recent years, our laboratory has accumulated a lot of experience in genetic engineering transformation of adenovirus, including vaccine research with adenovirus as vector, tumor gene therapy with suicide gene expression, adenovirus targeting and conditional replication, etc. In this process, we obtained a variety of intermediate vectors and virus packaging cell lines with detection signals, and developed mature technologies of vector construction, cell culture, virus packaging and purification. According to the sequence comparison, L 1, L2 and L4 of Ad37 and Ad43 are selected to replace the corresponding structures of Ad5 alone or simultaneously. At the same time, the escape ability of modified adenovirus vector to pre-existing immunity and the influence of different substitutions on adenovirus assembly were investigated. Good results have been achieved in this research work, and international cooperation is being carried out with Professor Dan baruch of Harvard University and School of Public Health of Johns Hopkins University.
6. Our laboratory has also made great progress in the research of non-viral vectors. Through organic synthesis and supramolecular assembly, a variety of reasonable functions were assembled into the DNA vaccine delivery system, and a series of glycosylated cationic polymer PLGA microspheres, dextran, mannose modified cationic polymer, gold nanoparticles and magnetic particles were designed and synthesized, thus improving the physical and chemical stability of DNA vaccine in vivo, and targeting dendritic cells through mannose modification to effectively simulate. So as to better target transfected cells and induce a strong immune response under the condition of low dose DNA vaccine. The research results in this field have published 5 papers in magazines such as Xiao, Biomaterials and JCR.
7. Several pre-clinical research and evaluation systems of vaccines have been established, including the establishment of animal models. By modifying HIV- 1, cells of rhesus monkeys and/or African green monkeys can be infected, thus establishing a cell model that can be used to evaluate vaccines and anti-HIV- 1 drugs. The standardized procedures and methods of neutralizing antibody evaluation system and cellular immunity evaluation system were established.
8. Established a standardized clinical research base for AIDS vaccine, established a long-term cooperative relationship with China Institute for the Control of Pharmaceutical and Biological Products and Guangxi Center for Disease Control and Prevention, and took the lead in developing and successfully completing the phase I clinical trial of AIDS vaccine in China.