Is Egg-based Vaccine Manufacturing on its Way Out?
The method selected for vaccine production is dependent on the virus or bacteria that you are vaccinating against. Since the technology was developed in the 1950’s egg-based vaccine manufacturing has been used to manufacture vaccines against influenza, mumps, rubella and others. Since that time cell culture techniques have been optimized for vaccine manufacturing and several vaccines are now manufactured using this technology including vaccines against influenza, rotavirus, polio and smallpox.
In a previous blog titled, “In preparation for the next pandemic…,” the dish discussed the advances being made in influenza vaccine manufacturing by implementing cell culture over egg-based production. Cell culture-based vaccine manufacturing for flu vaccines has many advantages over egg-based manufacturing, primarily the speed with which you can get a vaccine developed and manufactured (particularly important when dealing with an emerging pandemic). In addition, infection or contamination of the chicken flock or eggs themselves can wipe out an entire vaccine batch and further delay availability.
Despite the advantages in using cell culture for production of influenza vaccines, there are no current cell culture-based influenza vaccines approved in the United States (US). Baxter’s vero cell culture-produced Preflucel has been approved in Europe and was the topic of another blog on The Cell Culture Dish titled, “Cell Culture Flu Vaccine Approved in Europe…Is the United States Next?” Approval of Preflucel means that 13 European Union countries will make the vaccine available for the 2011-2012 flu season. Preflucel is already available in Austria and the Czech Republic.
Even though a cell culture-based influenza vaccine has not been approved in the US, there are other Food and Drug Administration (FDA) approved vaccines that utilize cell culture-based manufacturing. Vero cells are widely used in cell culture-based vaccine manufacturing and are ideal for this purpose because they are susceptible to a wide variety of the viruses that researchers are working to vaccinate against. The vero cell line is derived from kidney epithelial cells of the African green monkey and was first established in 1962.
The rotavirus vaccine is one example of cell culture-based vaccine manufacturing. Rotavirus is the most common cause of severe diarrhea in infants and children. In the United States, prior to vaccination, rotavirus caused 200,000 emergency room visits, 400,000 doctor visits and up to 60 deaths per year in children under five years old. It is extremely deadly in developing countries, with over 500,000 deaths of children under the age of five worldwide. Presently, there are two vero cell propagated vaccines approved in the US for rotavirus; Merck’s RotaTeq (approved by the FDA in 2006) and GSK’s Rotarix (approved by the FDA in 2008).
The current approved Inactivated Polio Vaccine (IPV) is also manufactured in vero cells. Polio was widespread in the US before vaccines were developed in the 1950’s. Through widespread vaccination, polio was eliminated from the western hemisphere in 1994, but a handful of countries still suffer from widespread polio outbreaks. The polio vaccine is still a recommended immunization for all children. The most common vaccine for polio in the US is IPOL, manufactured by Sanofi Pasteur and approved in 1987.
Sanofi Pasteur also manufactures the current vero cell propagated smallpox vaccine, ACAM2000, approved by the FDA in 2007. Routine vaccination eradicated small pox in the United States and regular vaccinations ended in the early 1970’s. Small pox was officially declared eradicated by the World Health Organization in 1980, but since then, concerns regarding bioterrorism have prompted the Center for Disease Control (CDC) to contract with Sanofi Pasteur to manufacture a new small pox vaccine in case of attack. This vaccine is available for military personnel, scientists working in small pox research, and others who are at high risk of infection. According to Sanofi Pasteur, they have provided over 196 million doses to the CDC for the national stockpile.
So with many good examples of cell-culture based vaccines, why continue with egg-based manufacturing? Is the primary reason that these vaccines are already approved and changing manufacturing would cause additional clinical trials and approvals at FDA? Is the reason the lengthy safety history that already exists with current egg-based vaccines? Or is it simply the old philosophy “if it isn’t broke, don’t fix it”? As new vaccines are developed and next generation versions of existing vaccines emerge, will vero cells be selected as the manufacturing method of choice or will another cell line take its place?