Why is it difficult to develop the world's first 14-valent HPV vaccine?
The formation of the correct structure of virus-like particles (VLP) is not only based on the correct gene sequence, but also the culture conditions and intracellular microenvironment are also crucial. Therefore, the expression and maintenance of VLP and the purification process to optimize its structural correctness are essential for the production of HPV vaccines. Technical threshold and main challenges.
Cervical cancer is one of the common gynecological malignancies, and most cervical cancers are caused by HPV virus infection.
Recently, Beijing Shenzhou Cell Biotechnology Group Co., Ltd. (hereinafter referred to as Shenzhou Cell) publicly released its research and development of the world's first 14-valent HPV vaccine into the clinic. This vaccine can quickly cover all 12 high-risk cancer-causing HPV virus types announced by the World Health Organization. And 2 HPV virus types that cause condyloma acuminatum most.
Compared with the imported 9-valent vaccine, what are the difficulties in developing this 14-valent HPV vaccine?
Compared with imported vaccines, what are the advantages of the 14-valent HPV vaccine?
A reporter from Science and Technology Daily interviewed relevant experts for this.
Expected to become "best in class" in the global market
"The'valency' of a vaccine represents the type of virus that the vaccine can prevent. Scientists have long discovered that the cross-reaction efficiency of HPV virus infection or HPV vaccine immunization is very low, such as HPV16 infection or HPV16-VLP immunization against other HPV subtypes. There is no protective effect, so there are vaccines that are improving and optimizing over time. The higher the vaccine price, the more types of preventable viruses, and the relative increase in the prevention rate of related diseases." Director, Deputy Director, Shenzhou Cell General Manager Tang Liming introduced.
At present, the European and American markets mainly use the 9-valent vaccine Gadaxiu 9 produced by Merck in the United States.
The diseases that Jiadaxiu 9 prevents include cervical cancer, vulvar cancer, vagina cancer, anal cancer and external genital warts caused by HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, HPV45, HPV52 and HPV58 infections.
Many international companies and R&D institutions have been trying to develop HPV vaccines with higher coverage, but no substantial progress has been made.
Tang Liming introduced: "Compared with the imported vaccine Jiadaxiu 9, the world's first 14-valent HPV vaccine has added 5 new high-risk cancer-causing HPV virus types, namely HPV35, HPV39, HPV51, HPV56 and HPV59. It will be used for prevention. Prevent cervical cancer and condyloma acuminata caused by HPV infection."
The reporter learned from public information that the 14-valent HPV vaccine has a better preventive effect on cervical cancer among Chinese women.
Based on the results and analysis of preclinical studies, it is predicted that the 14-valent HPV vaccine can increase the protective rate of cervical cancer from 90% of Jiadaxiu 9 to 96%. For individuals, the possibility of disease will be further reduced.
Experts pointed out that the 14-valent HPV vaccine has a higher coverage rate and is in line with the trend of HPV vaccine research and development. It is expected to become the "best-in-class" HPV vaccine in the global market and help gain more domestic and foreign market shares through differentiated competitive advantages.
Crossing the threshold of HPV vaccine production technology
Tang Liming said: "HPV vaccine development uses genetic engineering technology to produce HPV virus-like particles (HPV-VLP) without virus genes. Because HPV-VLP does not contain virus genes, HPV-VLP has no replication function, so it will not cause harm to humans. HPV virus infection risk, but HPV-VLP shell is very similar to HPV virus shell and has the same immunogenicity. Therefore, using HPV-VLP as vaccine antigen, after immunizing animals or humans, it can produce similar HPV virus infection The resulting immune response can enable the vaccinated person to gain immunity and reduce the risk of the vaccinated person's continuous HPV virus infection and the risk of cancer caused by it."
It is understood that the HPV vaccines currently on the market and under development are all based on the virus-like particle (VLP) technology formed by the L1 protein of recombinant HPV. Only VLPs with the same structure as natural viruses can induce immunogens that prevent diseases caused by HPV infection. sex.
The formation of the correct structure of VLP is not only based on the correct gene sequence, but also the culture conditions and intracellular microenvironment. Therefore, the expression and maintenance of VLP and the purification process to optimize its structural correctness are the technical threshold and main challenge for the production of HPV vaccines. .
The relevant person in charge of Shenzhou Cell said that the 14-valent HPV vaccine developed by the company relies on a series of industrialized technologies such as insect cell baculovirus production technology, purification technology, and virus-like particle disassembly technology, which are developed by the company, to produce virus-like particles. The whole process parameters have been systematically optimized, breaking through the technical difficulties and technical bottlenecks such as difficult expression of multiple HPV virus-like particles, low expression, imperfect particle assembly, and poor stability, and established all 14 important virus-like particles Efficient and highly similar production process technology.
The reliability of the process, high productivity, and the high degree of similarity in the process steps between subtypes greatly increase the competitiveness of the 14-valent HPV vaccine.
Public information shows that after more than ten years of preclinical research, Shenzhou Cell has established a number of key production technology for eukaryotic cells to produce high-quality HPV-VLP. Through the application of this technology, the feasibility of its 14-valent HPV vaccine development has been improved. Sexuality and competitiveness will help increase the use rate of HPV vaccine among the age-appropriate population and reduce the risk of cervical cancer and other cancers.
It is understood that the current production line of Shenzhou Cell that is expected to be used for vaccine production has leading advantages in process optimization and scale-up. The 14-valent HPV vaccine produced by it is expected to become the most cost-effective HPV vaccine in the world.
Contribute to the accelerated elimination of cervical cancer
Experts predict that after the 14-valent HPV vaccine is on the market, it is expected to provide the HPV vaccine with the highest coverage for women of the right age in my country.
Based on estimates of nearly 100,000 new cases of cervical cancer each year in my country, after large-scale vaccination of 14-valent HPV vaccine, it is expected that the number of new cases of cervical cancer each year will be reduced to no more than 4000 in the future, which has significant social and economic benefits.
The person in charge of Shenzhou Cell said that HPV vaccine has become one of the most popular drugs in the second-class vaccine market in my country. As more domestic companies participate in this vaccine industry, the market will not only get more vaccine supply, but also As people’s awareness of HPV vaccines and socio-economic conditions are improving day by day, there will soon be more female populations of the right age who tend to have more valence HPV vaccines with higher protection rates.
Tang Liming said: “The population of the right age can obtain a higher rate of HPV prevention and protection by vaccinating a single drug, which will help expand the choice of HPV vaccination and medication for the age-appropriate population, increase the willingness of the age-appropriate population to vaccinate, and improve the age-appropriate population’s HPV vaccine The utilization rate of cervix cancer reduces the risk of cervical cancer and other cancers."
The "Global Strategy for Accelerating the Elimination of Cervical Cancer" launched by the World Health Organization stated that by 2030, 90% of girls will have completed HPV vaccination before the age of 15; 70% of women will be screened by efficient testing methods before the age of 35 and 45; 90% of women diagnosed with cervical disease receive treatment.
In the future, the mass production of Shenzhou Cell 14-valent HPV vaccine will contribute to the implementation of this strategy that cannot be underestimated.
(Reporter Hua Ling)