Behind the prequalification of Sinovac's varicella vaccine, the 'SV-1 cell line' is indispensable

In a sense, the new crown vaccine has made the world realize that the rise of China's vaccine industry is a real emergence of Chinese vaccines in the world. But in fact, whether before or after the new crown vaccine, China's vaccine industry still has many products and achievements that are easy to overlook.

At the beginning of this month, the live attenuated chickenpox vaccine produced by Sinovac (Dalian) Vaccine Technology Co., Ltd., a subsidiary of Sinovac Holdings, passed WHO prequalification, and this vaccine launched in China in 2019 became the first prequalified chickenpox vaccine product in China.

Under the current situation of the high season of chickenpox epidemic and the insufficient supply of chickenpox vaccine in the world, Sinovac vaccine has once again gained international recognition and is expected to continue to play a greater role in the prevention and control of chickenpox disease in China and even the world.

Domestic demand for varicella vaccine remains unmet

In recent years, the new crown epidemic, in addition to allowing the people of the country to have a new understanding of vaccination, but also let several vaccine companies and various conventional vaccine products on the market get more opportunities to show their faces, CanSino, Zhifei, Sinovac do not talk much, but in addition to new crown vaccines, influenza vaccines and other respiratory infectious disease vaccines, chickenpox vaccines, HPV vaccines have also developed rapidly in recent years.

According to relevant data, in order to strengthen the prevention and control of chickenpox disease, the batch issuance of chickenpox vaccine in China has increased year by year in recent years, a total of 472 batches were issued in 2021, a year-on-year increase of 22%, and the batch issuance volume was 29.86 million bottles, if the lowest value of the general winning price (130-160 yuan / dose) is estimated, the domestic market size in 2021 has exceeded 4 billion yuan.

However, even such a high growth rate of the market status quo is not the end of the market demand for varicella vaccine.

After the domestic launch of chickenpox vaccine in 1997, the "one-shot" immunization procedure was adopted in various places. Until 2014, in order to effectively reduce the incidence and risk of regional outbreaks, some regional centers for disease control and prevention gradually began to allow the use of "two-shot" vaccination in accordance with WHO recommendations.

China's varicella vaccine has not yet been included in the national immunization program, and has only been included in the local immunization program in economically developed areas such as Shanghai and Tianjin. At present, the overall vaccination rate of varicella vaccine in China is not high, estimated by a single dose of immunization procedure (international authorities recommend the use of "two-shot method"), and the national average vaccination rate is only 61.10%, which is significantly different from Europe and the United States.

Today, 21 provinces and cities across the country have allowed the implementation of the "two-shot" immunization procedure for chickenpox vaccine by issuing guidelines on chickenpox vaccination. In the future, after the implementation of the "two-shot method" of chickenpox vaccine in more parts of the country, related vaccine companies may usher in greater demand space.

Sinovac's self-developed cell line has been internationally recognized

Different from other approved vaccine products before, the pre-certified Sinovac chickenpox vaccine uses Sinovac's independent intellectual property rights SV-1 cell line, which represents the "breakthrough" achievements of China's independent research and development of vaccines and has gained international recognition and far-reaching significance.

In the process of vaccine development, in addition to the virus strain, the most basic key raw material is to cultivate the cells of the virus. At present, the internationally accepted human cell line for vaccine antigen has been used for many years, and the widely used and latest 2BS human embryonic lung diploid cells were also isolated and established in 1973, and most cell lines will encounter problems such as high cell generation and unsatisfactory virus yield in the process of antigen preparation, and there are still restrictions on intellectual property rights for Chinese vaccine companies.

According to Song Lifei, general manager of Dalian Kexing, in order to ensure clear cell traceability, safety and stability, Sinovac varicella vaccine has chosen to use the younger and more vigorous SV-1 cell line independently developed and isolated by Sinovac since the beginning of the project in 2010, so as to maximize the growth of the virus and the quality control in the production process. After more than two years of research and efforts, Sinovac SV-1 cell line successfully passed expert demonstration in 2012.

SV-1 cell line, as one of the human diploid cell lines, limited survival generation is also its most important constraint, and in a study on the genetic stability and gene sequence difference site analysis of varicella-zoster virus (VZV) Oka strain on human diploid cell line SV-1", SV-1 was not only proved, the 33rd, 35th, 38th, 39th, and 48th generation virus homology obtained by VZVOka strain in its passage was 99.99%.

At the same time, in the comparison of homology of 38-generation strains of different cell lines, the VZV differential sites cultured by SV-1 cell lines were the same merger bases as standard vaccine strains (V.Oka) (single base on MRC-5 cell lines), which indicated that SV-1 could better maintain the genetic stability of VZVOka strains compared with MRC-5 cell lines.

Therefore, at least for VZVOka strains, its expression adaptability and genetic stability on SV-1 cells are good, and in some cases even exceed MRC-5 cell lines.

From the evaluation of vaccine safety and immunogenicity, relevant studies published in the journal Vaccine in June this year showed that a single dose of Sinovac live attenuated vaccine has good immune durability, and the antibody positive rate after the second dose is as high as 100%.

From the comprehensive view of a variety of data, Sinovac SV-1 cell line has quite good performance compared with WI-38, MCV-5, KMB-17, 2BS and other old cell line matrices, regardless of its expression adaptability and genetic stability, and even surpasses the expression of some cell lines, and has incomparable advantages in virus yield, survival generation control and intellectual property convenience.

Sinovac varicella vaccine passed prequalification, indicating that the international first recognition of vaccine research and development with SV-1 cell line as the matrix, is expected to provide more raw material choices and imagination space for the development of new vaccines worldwide.

China's vaccine innovation needs more "Sinovac"

Before Sinovac chickenpox vaccine, 7 vaccines in China have passed WHO prequalification and 3 vaccines have passed WHO emergency use authorization, which has provided more experience and confidence for Chinese vaccine companies to apply for qualification review, which also means that China's vaccine regulatory system is gradually maturing.

As mentioned before, the successful WHO prequalification of Sinovac varicella vaccine is an affirmation of enterprises, industries and even industries, and a true portrayal of "innovation changes the status quo and achieves new growth".

In the first seven months of this year, the value of China's offshore pharmaceutical business such as traditional Chinese medicine, biotechnology and R&D service outsourcing increased by nearly 20% year-on-year to 32.8 billion yuan, according to China's Ministry of Commerce. In 2021, the output value will reach 60.86 billion yuan, a year-on-year increase of nearly 25%.

Innovation has made China's biomedical industry a global alliance, and China's vaccine innovation will surely bloom more brilliantly in the world in the future.