Alternatives to Egg-Based Manufacturing
The right combination of antigens aside, alternatives to chicken egg-based manufacturing methods are needed, scientists say, to efficiently make enough vaccine to anticipate pandemics. It takes about one egg to make one dose of vaccine, meaning that around 100 million eggs are needed to create seasonal flu vaccines. And that’s one of the major limitations of the current process. If a strain of avian flu started infecting humans, for example, there might not be enough healthy chickens and healthy eggs to produce vaccines.
Transitioning to alternative vaccine production methods using mammalian cell lines or other innovative methods, experts say, will cut vaccine production times in the event of an outbreak. Egg vaccine production won’t cut it for a pandemic, either. Current data suggest that egg-based production yields of hemagglutinin (HA) expressed by H5N1 viruses generated by reverse genetics are only 30–40% of the average HA yield for seasonal influenza viruses while virus yields are similar to those obtained usually. This could have serious implications for inactivated influenza vaccine production in the event of a pandemic. There are also long-standing concerns that growth of human influenza virus in eggs can lead to the selection of antigenic variants which may be less efficacious.
But new vaccines produced in egg alternatives are entering the U.S. market, enabled largely by an inoculation of government capital. In 2012, the FDA approved Novartis’ Flucelvax®, manufactured in a mammalian cell line, the Madin-Darby canine kidney (MDCK) cell line, instead of chicken eggs.
Novartis had partnered with the U.S. Department of Health and Human Services, Biomedical Advanced Research and Development Authority (HHS, BARDA) for the development of the cell culture manufacturing technology, to produce the vaccine, as well as for construction of the state-of-the-art facility in Holly Springs, NC. Public/private investment in the technology development and facility came to $1 billion.
Next up was Protein Science Corporation’s Flublok®, approved by the FDA in January of this year. Flublok is described as the first trivalent influenza vaccine made using an insect virus (baculovirus) expression system and recombinant DNA technology. Flublok contains purified viral HA proteins produced in a continuous insect cell line (expresSF+®) derived from Sf9 cells of the fall armyworm, Spodoptera frugiperda, and grown in defined, serum-free medium.