Recently, the domestically produced nine valent HPV vaccine "Xinkening ® The approval of "9" for listing marks a crucial step for China in the field of high-end vaccine research and development. This vaccine was jointly developed by Professor Xia Ningshao's team from Xiamen University and Wantai Biotechnology. It took 18 years to overcome numerous technical difficulties and opened up an original path for China in the international vaccine technology system. Its birth is not only an industrial breakthrough, but also an enhancement of national public health capabilities. Faced with cervical cancer, a serious threat to women's health, China finally has an internationally advanced local protection plan.

Cervical cancer has long been in the forefront of the incidence rate of malignant tumors among Chinese women, with more than 100000 new cases each year. Although vaccines are the most effective primary prevention method, the heavy reliance on expensive imported vaccines in the past has resulted in a long-term coverage rate of 1% -3%. Especially in the Midwest region, many women find it difficult to receive the HPV vaccine. Xinkening ® The launch of 9, relying on a more affordable cost structure and a wider range of adaptable populations, is expected to further improve the public's acceptance and accessibility of vaccines, and contribute to the global goal of eliminating cervical cancer through Chinese solutions.

Behind this progress is not simply imitation or technology introduction, but technological innovation starting from the source. As early as 2002, Chinese researchers attempted to express HPV like viral particles in Escherichia coli, challenging the mainstream eukaryotic expression system at that time. This idea was once seen as' unconventional ', but Xiamen University and the Wantai Biotechnology team persisted in moving forward in the no man's land. From the launch of the first domestically produced bivalent HPV vaccine "Xinkening" to the successful approval of the 9-valent HPV vaccine, Chinese scientific research has made a leap from "following" to "running in parallel", and even "leading".

Science Relay and China's Path

Humanity is gradually conquering cervical cancer, and behind it lies a global relay that spans over a century. In the 1980s, German pathologist Hausen discovered that HPV16 and HPV18 were closely related to cervical cancer, leading humans to identify the mechanism of viral carcinogenesis. The real breakthrough in vaccines can be attributed to Ian Fraser from Australia and Chinese scientist Zhou Jian. In 1991, they first synthesized HPV virus like particles (VLPs) in experiments, opening up the possibility of vaccine development. Zhou Jian's inspiration came from his nighttime walk with his wife - it was the idea of the synergistic expression of L1 and L2 proteins that triggered the self-assembly of virus like particles. This achievement was ultimately published in Virology, becoming the starting point of the HPV vaccine industry.

The baton of technology quickly spread to China. Faced with the reality that expensive vaccines are difficult to popularize, Chinese research teams must find different technological paths. In 2002, Professor Xia Ningshao led a research team from Xiamen University and formed a joint team with Wantai Biotechnology to initiate the development of HPV vaccines. They did not adopt the globally mainstream eukaryotic expression system, but took a different approach and chose E. coli, a prokaryotic organism, as the expression system.

This is a system that has never been successfully applied to human vaccines globally. At that time, this idea was almost considered "unfeasible" by the entire academic community: how to make a bacterium that is far away from the human evolutionary path "listen" and produce viral proteins? How to remove endotoxins from proteins, fold them correctly, and smoothly stimulate immune effects? "Almost every step is blank. No one knows whether it will succeed or not, but its low-cost and high replicability potential perfectly meets the protection needs of hundreds of millions of women in China. From the beginning of the project, the R&D personnel have been constantly trying and making mistakes in thousands of experiments, but no one has given up halfway.

There is a significant gap between early investment and return. Even though there have been no commercial products released in the past 10 years since the establishment of the laboratory, and despite facing numerous financial constraints, the then chairman of Wantai Biotechnology, Zhong Suisui, has made the decision to continue investing and helped the Xia Ning Shao team overcome the most difficult stage. It is in this process that Xiamen University has established a mutual trust mechanism with enterprises: enterprises do not interfere with research directions, and research teams quickly respond to industrialization needs. This "industry university research collaboration" mechanism provides a rare channel for vaccines to go from basic research, technical validation to production registration, greatly compressing the research and development cycle.

Driven by both scientific research and capital, the bivalent HPV vaccine "Xinkening ®” Officially approved in 2019, phase III clinical trials have shown a 100% protection rate in preventing HPV16/18 related precancerous lesions. And this is precisely the starting point of HPV vaccine development. The team further completed the development of the nine valent HPV vaccine on the E. coli platform and continued to explore the "chimeric VLP", breaking through systemic challenges such as co expression and co purification of nine HPV types. This original path was later published in Nature Communications and was praised by the international academic community as a paradigm shift in reconstructing the logic of vaccine design.

From laboratory to clinical implementation

The success of the nine valent HPV vaccine lies in its closed-loop validation from technology to clinical practice. The comparative study of immunogenicity between similar foreign products and Xinkening was conducted in Ganyu, Jiangsu ® 9 with Gardasil ® Among women aged 18-26, 9 showed a completely consistent antibody positivity rate (100%), with five types even showing slightly better antibody concentrations. At the same time, the adverse reaction rate of the domestic vaccine group was 42.6%, which is basically equivalent to the 47.3% of the imported vaccine. There were no serious adverse events related to the vaccine, which verified its safety. The results of this study were published in the international medical journal The Lancet Infectious Diseases in 2023. This achievement was not only selected as one of the top ten medical technology news in China that year, but also made the international academic community realize that the E. coli expression system is not a low-level substitute, but another powerful technological path. This recognition of technological originality has earned unprecedented respect for Chinese biopharmaceuticals.

With the changes in the World Health Organization's (WHO) HPV vaccine immunization strategy and the increasing maturity of China's clinical design research system. Xinkening ® Expanding the original two needle method from 9-14 years old to 9-17 years old can provide convenience and reduce costs for more girls to receive the vaccine, making it easier for families to accept. These reliable and solid clinical trial data can not be separated from the hard work of researchers in Ganyu District, Jiangsu Province, Funing County, Lianshui County, Dazhu County, Sichuan Province, and Yuechi County. It is precisely out of the hope that the domestic nine valent HPV vaccine will come into the market as soon as possible, so that more Chinese people can afford and use it with confidence, which supports researchers to overcome many difficulties during the epidemic, and finally complete the clinical trial with quality and quantity guaranteed and achieve ideal phased success.

Xinkening ® The "original chain model" based on 9 institutes - from antigen design to independent development of clinical pathways, enables them to have complete intellectual property rights, without relying on any foreign technology authorization, and has independent export and registration capabilities. This advantage has also enabled China to achieve significant breakthroughs in vaccine technology sovereignty, laying the foundation for future vaccine "going global".

Let the world use Chinese vaccines

The launch of the nine valent HPV vaccine coincides with a key milestone in China's promotion of the "Action Plan to Eliminate Cervical Cancer (2022-2030)". High cost and low coverage have long constrained the popularization of vaccines. Public information shows that Xinkening ® The pricing of 9 is expected to be less than half of the imported products; By combining the two dose strategy, the procurement cost of the public health system can be significantly reduced. As of now, several provinces and cities such as Hainan, Jiangsu, and Guangdong have included domestically produced HPV vaccines in the free vaccination project for the benefit of the people. The vaccination rate in some cities has exceeded 90%, and China is gradually becoming a model for universal vaccination from a vaccine weak country.

At present, the nine valent HPV vaccine has not been exported, but the bivalent HPV vaccine Xinkening ® It has passed WHO PQ certification in 2021 and entered the United Nations system procurement catalog, becoming the fourth HPV vaccine in the world to obtain WHO PQ certification. As of now, market access has been obtained in 21 countries, 8 countries have been included in national immunization plans, and millions of doses of universal vaccination have been achieved in countries such as Nepal, Angola, and Thailand. Behind this is not only recognition of product quality, but also the comprehensive output of Chinese vaccines from compliance, production capacity to technical standards.

Nowadays, the annual production capacity of Wantai Biotechnology's bivalent HPV vaccine has reached 30 million units, and the approved production line capacity of the 9-valent HPV vaccine is 20 million units. In the channel segment, it has covered 31 provinces and cities and over 97% of districts and counties in China. Beyond accessibility, the research team has initiated the development of phase III clinical trials and even a new generation of 21 valent HPV vaccines for male indications. Based on structural vaccine design, this vaccine only requires 8 types of virus particles to cover 21 types of HPV, and is expected to define the "final form of HPV vaccine" globally.

Perhaps just as Zhou Jian's spiritual inspiration flashed during his walk that night, the science that truly changed the world was not a single burst of genius, but a long-term tradition passed down from generation to generation. It cannot be ignored that the long-term mutual trust and cooperation between Professor Xia Ningshao's research team at Xiamen University and Wan Tai Biotechnology led by Zhong Suisui is also an inevitable factor beneath the surface coincidence.

From a light in the laboratory to the HPV vaccine going global, Wantai Biotechnology and Chinese scientific research are working together to embark on a longer-term public health revolution.