Vaccination with Vero cell-produced vaccine does not cause cancer

From: Meng Shengli Bowen

About the author: Doctor, researcher, Wuhan Institute of Biological Products Co., Ltd. The editorial board of Journal of Applied Virology, Infection, Genetics and Evolution, PLOS Neglected Tropical Diseases, International Journal of Public Health and Epidemiology, Disease Surveillance, Issues in Biological Sciences and Pharmaceutical Research, International Journal of Biological Products and other magazine reviewers have long been committed to rabies antigen, antibody detection, rabies vaccine clinical effect evaluation and rabies related knowledge popularization.

We know that hepatitis B vaccine can prevent liver cancer caused by hepatitis B virus, and HPV vaccine can prevent cervical cancer caused by related HPV virus. In addition to vaccines to prevent infectious diseases, in recent years, vaccines for the treatment of cancer have made important progress. Many vaccines have entered clinical research. The prostate cancer vaccine Provenge approved by the US Food and Drug Administration is the first therapeutic cancer vaccine on the market. However, there are always some anti-vaccine people who attack and denigrate the value of vaccines. For example, there is a potential risk of advocating Vero cells on the Internet. Of course, the most important thing is that Vero cells have potential tumorigenicity or carcinogenicity. This "potential", when ordinary people look at it, their first impression is that Vero cells may cause cancer or cause cancer under certain conditions, this makes many people who are vaccinated with vaccines produced by Vero cells very afraid. Vaccination is to prevent diseases caused by corresponding pathogens of vaccines produced by Vero cells (rabies vaccine, inactivated Japanese encephalitis vaccine, inactivated polio vaccine, etc.). However, due to misunderstanding of network rumors, Vero cells are worried about cancer after vaccination. Whether Vero cells are carcinogenic can be completely confirmed by tests, and some people have confirmed by experiments that Vero cells within 250 generations have no tumorigenicity in vivo or in vitro. As far as I know, no company has more than 200 generations of Vero cells producing vaccines at home and abroad, most of which are within 150 generations. Since Vero cells are passaged cells, they can be passaged indefinitely in theory. As to whether they have tumorigenicity after 300 and 1000 generations, there is no test report at present. Of course, such tests are meaningless. In reality, no enterprise will amplify Vero cells to 300 and 1000 generations before inoculating viruses and preparing corresponding vaccines. So we can be sure that Vero cells in the world known to be approved for the production of vaccine generation, the production of vaccine will never cause cancer, there is no "potential".

At present, the rabies vaccines on the Chinese market belong to cell culture vaccines, but the cells used in different manufacturers to produce vaccines are different, mainly Vero cells, human diploid cells, chicken embryo cells and hamster kidney cells.
Among these cells, human diploid cells have a limited number of passages in an in vitro environment, and require higher culture conditions, so the cost for vaccine production is higher. Vero cells are cells that can be passed on many times, with strong reproductive ability, extremely long life span, and basically no limit on the number of passages. They are very suitable for large-scale bioreactor culture, and can achieve large-scale and good consistency between batches. Within the known non-carcinogenic generation, it is to exclude potential carcinogenic risks. Think about it, how can countries put a product with potential carcinogenicity on the market? Absolutely impossible. Vaccines produced with Vero cells on the market are definitely not carcinogenic.

According to the analysis of the results of the various vaccines produced by Vero cells actually used by billions of people around the world, the cells are actually quite safe, and there is no definite evidence of cancer. But in theory, there is a potential risk of cancer after cells are passed on to unlimited generations, and this risk is only speculation.

The regulation of vaccines in the United States is one of the most stringent in the world. In September 2009, the United States first approved the marketing of vaccines produced by Vero cells-Sanofi Pasteur's smallpox vaccine produced by Vero cells. In August 2012, the United States approved the DTaP-HepB-IPV combination vaccine produced by GSK, of which IPV is produced using Vero cells. In May 2013, FDA has approved Vero cell Japanese encephalitis inactivated vaccine produced by IntercellBiomedical (Livingston, United Kingdom) company for sale, which also shows that FDA has approved Vero cell vaccine to be safe through scientific evaluation for many years. The vaccinated population is 2 months old -16 years old, a total of 2 doses. Subsequently, in June 2013, the United States approved MERK's oral 4-valent rotavirus vaccine produced by Vero cells. China is a major vaccine producer, and our country has the most stringent requirements for vaccine quality. At present, the vaccines prepared with Vero cells in China also include IPV, inactivated Japanese encephalitis vaccine, hepatitis A vaccine, EV71 vaccine, hemorrhagic fever vaccine and the latest new crown vaccine on the market, etc., covering children's planned immunization vaccines, non-planned immunization vaccines and adult vaccines, providing more choices for the prevention of a variety of infectious diseases.

China began to recognize WHO and European standards about 20 years ago, allowing vaccines made with Vero cells to be imported or produced domestically. But since 2010, China has raised the standard for detecting residual DNA in Vero cell vaccines. The Chinese Pharmacopoeia (2010 edition) stipulates that the DNA residue of rabies vaccine should not be higher than 100pg/dose (I .e. 0.1 ng), which is 100 times stricter than the European and WHO standards (10ng/dose). The results of the statistical analysis demonstrated that Vero cells practically did not cause carcinogenicity compared to the control, with a defined passage number and residual DNA content.

The French Pasteur Verbo rabies vaccine is produced using Vero cells and has been in China since 2005. As China raised the testing standards for DNA residues in 2010, the Verbo vaccine had to be withdrawn from the Chinese market.

At present, most of the rabies vaccines on the Chinese market are produced in China with Vero cells, which are produced according to the new standards stipulated in the 2015 edition of the Chinese Pharmacopoeia.

Vero cell line was cultured from normal African green monkey kidney tissue in 1962, passed to ATCC (American Model Culture Collection Bank) for preservation in the 113 generation, passed to ATCC for establishment in the 121 generation, and passed to WHO for establishment in the 124 generation. At present, WHO's Vero cell bank is stored in ATCC in the United States and ECACC (European Cell Culture Collection Center) in Europe. The main cell bank is 134 generations, and the maximum working cell generation for production is 150 generations. Studies have shown that Vero cells passaged to the 169 generation is still not carcinogenic. The joint identification of 10 laboratories around the world shows that the cells can meet the WHO requirements for the production of biological products for continuous cell lines in no more than 169 generations. Researchers at the Beijing Institute of Biological Products have used tests to prove that Vero cells are not tumorigenic for passage 250.

If the virus is propagated using the Vero cell line, the European Pharmacopoeia, 8th Edition, and the WHO stipulate that the residual host cell DNA content should not be higher than 10ng per 1 human dose of vaccine. Billions of people in Europe and Asia have used various vaccines (including the rabies vaccine) produced using Vero cells over decades. The results of the statistical analysis of the usage records demonstrate that Vero cells do not actually increase their carcinogenicity compared to the control, with a defined passage number and residual DNA content. Vaccines produced with the cells are actually safe and do not cause cancer. The WHO has supported the production of various vaccines with Vero cells for many years. WHO recently officially affirmed and recommended the use of Vero cells to produce vaccines.

For some time, the WHO raised the standard for residual DNA in this cell to 100pg/dose, resulting in an immediate increase in the price of related vaccines in the world and even a serious market shortage. After weighing the pros and cons, WHO has restored the standard of DNA residue to the original standard of 10ng/dose in recent years, believing that the advantages outweigh the disadvantages.

The amount of rabies vaccine used in China is more than 10 million people every year. Apart from Vero cells, it is impossible to produce as many vaccines as the market needs with other cells. Therefore, the carcinogenic risk of Vero cells, which only exists in theory and has not been verified by actual data, should not be overemphasized to avoid misunderstanding and panic.

This blog post was written by Yan Jiaxin, a teacher in Meng Shengli, "Can rabies vaccine cause cancer?"

(http://blog.sciencenet.cn/blog-347754-560412.html) is compiled on the basis of, and some contents have been updated. I would like to express my gratitude here.

References:

1.http://www.cdc.gov/vaccines/acip/recs/GRADE/je-child.html

2.http://www.cdc.gov/vaccines/acip/recs/GRADE/je-child.pdf

3.http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/B/excipient-table-2.pdf

4. Li Ailing, Wang Hongyan, Zhang Yuelan, etc. Detection of tumorigenicity of Vero cells during passage [J]. Chinese Journal of Microbiology and Immunology, 2011,31(5):456

5.http://www.answers.com/topic/vero-cell