Tumorigenic and Tumor-Derived Cells Used to Make Vaccines
The urgent demand for vaccines against emerging diseases has necessitated the use of novel cell substrates. These include tumorigenic cells such as MDCK and CHO cells (for influenza virus vaccines), 293 and PER.C6 cells (for adenovirus-vectored HIV-1 and other vaccines), and tumor-derived cells such as HeLa cells (aborted fetal tissue for HIV-1 vaccines).
The use of tumorigenic and tumor-derived cells is a major safety concern due to the potential presence of viruses such as retroviruses and oncogenic DNA viruses that could be associated with tumorigencity, Therefore, detection of persistent, latent DNA viruses, and endogenous retroviruses in vaccine cell substrates is important for vaccine safety, particularly in the development of live viral vaccines, where there are no or minimal virus inactivation and removal steps during vaccine manufacturing.
Virus-based vaccines are made in living cells (cell substrates). Some manufacturers are investigating the use of new cell lines to make vaccines. The continual growth of cell lines ensures that there is a consistent supply of the same cells that can yield high quantities of the vaccine.
In some cases the cell lines that are used might be tumorigenic, that is, they form tumors when injected into rodents. Some of these tumor-forming cell lines may contain cancer-causing viruses that are not actively reproducing. Such viruses are hard to detect using standard methods. These latent, or "quiet," viruses pose a potential threat, since they might become active under vaccine manufacturing conditions. Therefore, to ensure the safety of vaccines, our laboratory is investigating ways to activate latent viruses in cell lines and to detect the activated viruses, as well as other unknown viruses, using new technologies. We will then adapt our findings to detect viruses in the same types of cell substrates that are used to produce vaccines. We are also trying to identify specific biological processes that reflect virus activity.
These methods will enable FDA scientists to help manufacturers to determine whether their specific cell substrate is safe to use for vaccine production.