Application Of Tangential Flow Filtration in Hepatitis B Vaccine Production Process
Infectious diseases have been a great threat to human survival and health since ancient times. The invention of vaccines has effectively cut off the spread of infectious diseases between people and enhanced human resistance to pathogenic microorganisms, so vaccines have become the most advantageous weapon for human prevention of infectious diseases. The invention of hepatitis B vaccine is a great achievement of vaccine research. Hepatitis B virus (HBV) infection is a worldwide epidemic, according to the World Health Organization (WHO) estimates that about 296 million people worldwide are chronically infected with HBV; Approximately 820,000 people worldwide die each year from diseases associated with HBV infection. HBV infection is an important etiology and progression factor of liver cancer. 84% of liver cancer in China is caused by HBV infection. In the face of such a fierce hepatitis B virus, the hepatitis B vaccine invented by humans has effectively prevented the spread of the hepatitis B virus. According to statistics, since the hepatitis B vaccination, whether it is developed or developing countries, the hepatitis B virus carrying rate has been greatly reduced, especially the effective control of mother-to-child transmission of hepatitis B virus.
The hepatitis B vaccine is widely used in children and adults. The hepatitis B vaccine used by children accounts for about 84% of the total. The global hepatitis B vaccine market size is approximately 6.6 billion yuan (RMB) in 2022 and is expected to reach 7.5 billion yuan in 2030, with a compound annual growth rate (CAGR) of 1.8% during 2023-2030. Over the past few years, the global hepatitis B vaccine market has developed steadily, with an average growth rate of -0.32%. The Asia-Pacific region is the world's largest consumer of hepatitis B vaccines, with a consumer market share of nearly 50% in 2019. The Middle East and Africa, second only to Asia Pacific, is the world's second largest consumer region, with a consumer market share of nearly 30%.
Hepatitis B virus (HBV)
Hepatitis B virus (HBV) is a hepatotropic DNA virus, which is composed of envelope and nuclear shell, and has strong infectivity. The main site of invasion is human liver, which can lead to hepatitis B, liver fibrosis, liver cancer and other related diseases after infection. Hepatitis B virus has strong survival ability in vitro, has high adaptability to dry and low temperature environment, and can survive more than 7 days at 37℃. The most commonly used alcohol and ultraviolet light can not inactivate it. There are three main ways of transmission of hepatitis B virus.
Vertical transmission: also known as mother-to-child transmission, if suffering from hepatitis B, and the virus replication rate is very high in the birth of the mother, the virus may pass through the placenta, milk, blood to the fetus, so it is recommended that pregnant mothers, as far as possible to control the hepatitis B virus pregnancy and birth.
Blood transmission: It may be transmitted from hepatitis B patients to the damaged skin of healthy people through blood transfusions, sharing needles, toothbrushes, razors, etc., and then it will enter the blood of normal people.
Sexual transmission: Hepatitis B virus, like HIV, can be transmitted through sexual contact and through bodily fluids.
Hepatitis B vaccine
Hepatitis B vaccine is a special drug used to prevent hepatitis B. After vaccination, the immune system can stimulate the production of protective antibodies, this antibody exists in human body fluids, once the hepatitis B virus appears, the antibody will immediately act to clear it, prevent infection, and do not harm the liver, so that the human body has the immunity to prevent hepatitis B, so as to prevent hepatitis B infection. Hepatitis B vaccine is the most effective way to prevent hepatitis B virus infection.
Hepatitis B vaccine is divided into two categories: blood-derived hepatitis B vaccine and genetic engineering hepatitis B vaccine, of which genetic engineering hepatitis B vaccine is divided into yeast hepatitis B vaccine and CHO hepatitis B vaccine. At present, China mostly uses genetic engineering hepatitis B vaccine, and the proportion of yeast hepatitis B vaccine in 2019 is about 97%.
Hepatitis B vaccine is an effective weapon to prevent hepatitis B. Because HBV cannot grow and multiply in vitro tissue cells, it is impossible to make a vaccine by traditional methods. Since Blumberg's discovery of HBsAg in serum in 1964, studies have found a maximum of 1013 HBsAg particles per milliliter of serum, and there are more asymptomatic carriers in the population, which provides conditions for the manufacture of blood-derived vaccines. In the late 1970s, Maupas and Hilleman developed a hepatitis B subunit vaccine. The experimental results confirmed that the vaccine played a good role in preventing hepatitis B virus infection. Countries have been preparing hepatitis B vaccine, mainly using the blood of asymptomatic carriers of hepatitis B virus, this vaccine is the first generation of hepatitis B vaccine, also known as blood-derived hepatitis B vaccine. In 1979, China also developed a subunit experimental vaccine, which proved safe and effective in population immunization. Due to the development of molecular biology, the way of preparing hepatitis B vaccine by genetic engineering has been opened up. Its basic principle is to clone HBSAG gene into plasmid, then transfect into yeast cells or mammalian cells, and express the surface antigen through gene recombination and cell culture. The hepatitis B vaccine produced by genetic engineering method can get the same immune effect as the blood-derived vaccine.
Hepatitis B vaccine production process
Tangential flow filtration technology has the advantages of mild and low shear force, flexible operation, long product life and low cost, and easy to scale up. It solves the two technical problems of easy membrane blocking during particle concentration and easy aggregation due to shear force sensitivity, and is widely used in biopharmaceutical and life science research fields such as vaccines. From the production process of hepatitis B vaccine, it can be seen that both the production of blood hepatitis B vaccine and the production of genetically engineered hepatitis B vaccine are inseparable from tangential flow filtration technology, and tangential flow filtration runs through the entire production of hepatitis B vaccine.
1 Blood-derived hepatitis B vaccine: Blood-derived hepatitis B vaccine is made from the plasma of asymptomatic hepatitis B carriers, after concentration and purification, the effective antigen HBsAg is extracted, and the adjuvant aluminum hydroxide is added after inactivation. The hepatitis B vaccine can prevent and control hepatitis B after being inoculated to human body. The comprehensive purification technology of high titer plasma raw material by multiple zonal ultracentrifugation, ultrafiltration combined with enzyme treatment and the three-step inactivation process of gastroenzyme, urea and formaldehyde were established.
2 Genetically engineered hepatitis B vaccine: Genetically engineered hepatitis B vaccine is a hepatitis B surface antigen (HBsAg) subunit vaccine, which uses modern biotechnology to construct the surface antigen expression gene of hepatitis B virus into a plasmid, cloned into beer yeast or CHO cells (Chinese hamster ovary cells), and the recombinant yeast or CHO cells are cultured to express the hepatitis B surface antigen subunit. After fermentation, through cell fragmentation and a series of microfiltration, ultrafiltration, silica gel adsorption, elution and other processes, and then through hydrophobic chromatography, the purity of the antigen protein of the product can reach more than 99%.
About Guidling
Guidling Technology is a national high-tech enterprise focusing on biopharmaceuticals, cell culture, purification and concentration of biomedicine, diagnosis and industrial fluids. We have successfully developed centrifugal filter devices, ultrafiltration & microfiltration cassettes, virus filter, TFF system, depth filter, hollow fiber, etc. Which fully meet the application scenarios of biopharmaceuticals, cell culture, and so on. Our membranes and membrane filters are widely used in concentration, extraction and separation of pre-filtration, microfiltration, ultrafiltration and nanofiltration. Our many product lines, from small, single-use laboratory filtration to production filtration systems, sterility testing, fermentation, cell culture and more, meet the needs of testing and production. Guidling Technology is looking forward to cooperating with you!
