Knock on the "gate" for the development of a 20-valent vaccine
——The story behind the launch of the first domestic cervical cancer vaccine
Our correspondent Xie Kaifei Correspondent Ouyang Guilian
Recently, the first domestically produced cervical cancer vaccine was approved and will be officially launched. Vaccination can be scheduled from May. After 18 years, China has become the third country in the world to achieve independent supply of HPV vaccine after the United States and Britain.
Just on March 16 this year, this domestic cervical cancer vaccine passed the PQ certification of the World Health Organization and officially entered the technical review stage. At present, Indonesia, Pakistan, Bangladesh and other countries have signed cooperation agreements for the introduction of domestic cervical cancer vaccines.
Break the international monopoly and develop an innovative vaccine development technology system
Cervical cancer is cancer that can be prevented by vaccination and cervical cancer screening. As a country with a high incidence of cervical cancer, China faces the dilemma of a gap of 1 billion cervical cancer vaccines.
Prior to this, only three cervical cancer vaccines were available worldwide, so imported cervical cancer vaccines have maintained high prices. The development of high-quality and cheap domestic cervical cancer vaccines has become China's major livelihood needs. In 2002, Xiamen University and Yangshengtang started the research on cervical cancer vaccine.
However, foreign pharmaceutical giants have been involved in this field as early as 1990, and built a comprehensive patent protection system around cervical cancer vaccine research. Facing the "blocker tiger" on the road to innovation, the research team took a different approach and decided to start with the antigen expression technology and adopt a unique new vaccine development technology system-E. coli prokaryotic expression system.
The system has high safety, low production cost and fast production speed. However, compared with the eukaryotic expression system adopted abroad, because E. coli does not have the advanced functions of "post-translational modification" of this system, "the statement that E. coli cannot be used as a genetically engineered vaccine" also became the vaccine world at that time. The general view is that there has been no precedent for success at home and abroad.
An unknown young Chinese team who has never made a vaccine is good enough to make imitations, but can it also make original innovations from technology platforms to products with a cycle of more than 10 years? The research team has always been questioned.
No retreat, based on the experimental data and the beliefs in their hearts, they withstood the pressure and conducted research silently on the cold bench.
Be the first to knock on the "gate" for the development of the third generation cervical cancer vaccine
From a professional point of view, as an unenveloped DNA virus, the HPV virus shell is composed of two proteins, L1 and L2. Under appropriate conditions, L1 protein can form pentamers, and 72 pentamers self-assemble into "virus-like particles".
To play the role of a vaccine, the L1 protein antigen expressed by E. coli needs to form L1 protein pentamers in vitro and assemble into virus-like particles similar to natural viruses. However, in this process, how to make the cysteine of multiple L1 proteins can be accurately paired with each other to form the correct disulfide bond, and the correct formation of pentamers has become a "thorny" problem.
To this end, the research team spent a total of 7 years to overcome all technical difficulties and complete the laboratory and preclinical studies of cervical cancer vaccines.
The research team did not pursue high "prices" from the beginning, but adopted the strategy of "generational research" by integrating domestic demand and its own technology maturity. At present, the second-generation cervical cancer vaccine (nine-valent) has completed Phase II clinical trials, and will soon begin Phase III clinical trials.
At the same time, the research team developed structural vaccinology technology and took the lead in knocking on the "gate" for the development of the third generation cervical cancer vaccine (20-price), with a protection rate of more than 99%.
Today, the research team has filed official patent applications in China for the first-generation two-valent, second-generation nine-valent, and third-generation twenty-valent cervical cancer vaccines. It is also in the United States, Britain, France and other countries. He obtained 64 patent rights and successfully built an independent patent protection network. Based on independent intellectual property rights, on September 6, 2019, Yangshengtang Xiamen Wantai successfully signed a global cooperation agreement with global vaccine giant GlaxoSmithKline to develop a new generation of cervical cancer vaccine. Chinese cervical cancer vaccine technology will go global.