Cell-Based Flu Vaccines

On November 20, 2012, the U.S. Food and Drug Administration (FDA) approved the use of Flucelvax,  the first U.S.-licensed (trivalent inactivated) influenza vaccine manufactured using cell culture technology for use in people 18 years and older. In May 2016, FDA approved a quadrivalent (four component) inactivated formulation of Flucelvax [193 KB, 19 pages] for use in people 4 years and older. In August 2016, FDA approved the use of cell-based candidate vaccine viruses in the production of Flucelvax.

What are cell-based flu vaccines?

‘Cell-based’ refers to how the flu vaccine is made. A cell-based flu vaccine is made by growing viruses in animal cells, which is a different manufacturing process than the traditional egg-based manufacturing process that is used to produce most flu vaccines. While the production processes are similar, a significant difference is that the influenza viruses used in the cell-based vaccine are isolated and grown in cultured cells of mammalian origin instead of in hens’ eggs.

Why has a cell-based flu vaccine been developed?

A cell-based flu vaccine was developed as an alternative to the egg-based manufacturing process. Cell culture technology is potentially more flexible than the traditional technology, which relies upon adequate supply of eggs. In addition, the cell-based flu vaccine that uses cell-based candidate vaccine viruses (CVVs) has the potential to offer better protection than traditional, egg-based flu vaccines as a result of being more similar to flu viruses in circulation. For more information, see the questions “How is the cell-based vaccine manufacturing process different than the traditional egg-based manufacturing process?” and “What is the significance of FDA approving cell-based candidate vaccine viruses for use in the Flucelvax cell-based vaccine?”

How is the cell-based vaccine manufacturing process different than the traditional egg-based manufacturing process?

In place of fertilized chicken eggs, the cell-based vaccine manufacturing process uses animal cells (Madin-Darby Canine Kidney, or MDCK) in liquid culture as a host for the growing influenza virus. In the past, FDA required that egg-isolated candidate vaccine viruses be used in the production of flu vaccine. However, on August 31, 2016, FDA approved the use of cell-isolated candidate vaccine viruses in the production of Flucelvax, the only licensed cell-based flu vaccine in the United States.

What is the significance of FDA approving cell-based candidate vaccine viruses for use in the Flucelvax cell-based flu vaccines?

Growing influenza viruses in eggs can introduce changes (i.e., egg-adapted changes) that can have important implications for the body’s immune response to vaccination. For example, these egg-adapted changes could cause the body’s immune system to produce antibodies that are less effective at preventing disease caused by the specific flu viruses in circulation. FDA approval of cell-grown CVVs will reduce egg-adapted changes and may result in vaccines containing virus that is more “like” wild-type circulating viruses. Therefore, the FDA’s approval of cell-based candidate vaccine viruses has the potential to improve the effectiveness of cell-based flu vaccines.

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What are the possible benefits of using cell-based influenza vaccines?

A major advantage of cell culture technology includes the potential for a faster start-up of the vaccine manufacturing process in the event of a pandemic. The cells used to manufacture Flucelvax are kept frozen and “banked.” Cell banking assures an adequate supply of cells is readily available for vaccine production. Growing the influenza viruses in cell culture for the manufacture of Flucelvax is not dependent on an egg supply. Also, as described above, cell-based flu vaccines that are produced using cell-based candidate vaccine viruses have the potential to improve the effectiveness of cell-based flu vaccines (compared to egg-based flu vaccines) by eliminating the kinds of egg adaptations that occur in egg-manufactured flu vaccines.

What were the results of the clinical trials using cell-based technology?

Clinical studies demonstrate that Flucelvax is safe and effective for use in individuals 4 years of age and older. General reactions to Flucelvax were typical of those seen with other injectable influenza vaccines. Pain, redness and soreness at the injection site and headache and fatigue were the most common reactions.

Has cell-based technology been used before?

Cell culture technology has been used to produce other U.S.-licensed vaccines, including vaccines for rotavirus, polio, smallpox, hepatitis, rubella and chickenpox.

Cell-based flu vaccines have been approved for use in multiple European countries.