Human Cell Lines used in Vaccines

To create a vaccine you need a method to propagate quantities of the bacterium or virus. In the early days of vaccine production, calves were used to produce cox pox virus and even into the mid 20th century pathogens continued to be grown in live animals or animal cells. After the discovery of viruses like the SV40 in animal cells, focus shifted to the viability of human cell lines in the late 60’s. WI-38 and MRC-5 are the two main human cell lines used in vaccine development, with Hepatitis A, rubella, varicella, zoster and MMR being the most commonly used vaccines created with the use of these lines.

Influenza vaccines are still made today using hen’s eggs with the embryo removed, a technology developed in the forties. This method is rather slow and dependant on a continuous supply of hen’s eggs, and is not compatible with the industry’s need to produce vast quantities of vaccines in a short space of time assuming that some of those mythical pandemics eventuate. But human cell lines also have limitations; they will only replicate a certain number of times before dying. This is where tumour cells come in; cancer is all about limitless multiplication of cells which is a handy attribute for vaccine makers.  In the lab this infinite replication translates to a higher yield at a lower cost.

In 2001 a paper on the FDA website outlined some concerns about the use of human cancer cells or designer cells as they called them, for manufacturing viral vaccines.

“Residual DNA in vaccines derived from tumorigenic cells….can pose potential risks to the vaccine recipient in two respects: oncogenicity and infectivity” Oncogenicity is the ability to induce tumours, and infectivity is the capacity to spread disease. Neither of which would seem to be desirable traits.

“..the incoming DNA could integrate into the host genome in certain genes…. tumor suppressor genes, which are involved in cell cycle control among other cellular processes. Loss of function of tumor suppressor genes has been associated with certain human tumors.” Fully functional tumor suppressor genes are something that I think we all would like to keep.

Currently the FDA have an industry guidance document which require the manufacturers to demonstrate that the final product is free of the introduced viral sequences. But get this – “Tumorigenic or tumor-derived cell lines for which the mechanism of transformation is unknown will require additional testing to ensure the absence of potential transforming and oncogenic agents”. Surely it will be more difficult to rid the product of something when you are not sure exactly what it is you’re looking for.

Another problem is the presence of adventitious agents ie any type of virus, bacteria, mycoplasma or TSE (mad cow disease) that you didn’t know was likely to be in there. SV 40 found in early polio vaccines is an example.

In 2013 a company called PaxVax gained FDA approval for A549 cell substrate in human clinical trials. A549 was produced from the culturing of a cancerous human lung tissue. PaxVax plan to produce the H5 Pandemic flu vaccine using this cell line. So don’t forget to rush out and get your flu shot next winter, chances are it might be made using this technology.

References

Current and Emerging Cell Culture Manufacturing Technologies for Influenza Vaccines

Medical research: Cell division

“Designer” Cells as Substrates for the Manufacture of Viral Vaccines

A549: Taking Viral Vaccine Production to the Next Level

Matrix and Backstage: Cellular Substrates for Viral Vaccines

Human Cell Strains in Vaccine Development

vaccine excipients

Cell-Culture-Based Vaccine Production: Technological Options

Guidance for Industry

Characterization and Qualification of

Cell Substrates and Other Biological

Materials Used in the Production of Viral

Vaccines for Infectious Disease

Indications

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