Plasmid DNA–Based Vaccines: Combating Infectious Diseases

A comparison of plasmid DNA-based vaccines with vaccines developed from egg and cell-based methods
Aug 02, 2007


The traditional method for developing a vaccine uses substrates isolated from chicken eggs or mammalian cells. This method has several drawbacks that could pose many problems. The first major issue is the time taken to develop a vaccine using this method, which could be longer than six months. The nature of the disease agent can present significant challenges to cell- and egg-based production depending on the species and strain of the agent. Moreover, there is a concern that people with allergies to eggs may also react negatively to an egg-based vaccine. Using modern plasmid DNA-based vaccines to combat infectious diseases is an alternative to traditional egg-based and mammalian-based vaccines. This article compares these two methods of developing and producing vaccines.

The use of vaccines to fight infectious diseases is not a new practice. Vaccines have been around for over two hundred years with one of the first documented being the vaccine for smallpox, which was developed and introduced in the 1790s. Over the years, science and medicine have made great strides in developing and producing numerous successful vaccines to combat various diseases. The smallpox vaccine developed by Jenner was prepared by taking scrapings of cowpox lesions directly from infected cattle. The two polio vaccines developed in 1952 by Jonas Salk and Albert Savin used a revolutionary new technique that allowed the propagation of polio virus in cultured monkey kidney cells.1 Today, effective vaccines for human diseases are produced by a variety of methods.

Developing Egg- and Cell-Based Vaccines

Table 1. The primary techniques for vaccine production 4
Traditional methods for developing and producing vaccines use substrates from either embryonated chicken eggs or mammalian cells. The primary techniques for vaccine production used today are shown in Table 1. The table shows that chicken embryos are primarily used for vaccines for viral diseases. The production of vaccines using fertilized eggs has over a fifty-year history. Though this method has been successful in the fight against numerous diseases including influenza, measles–mumps–rubella (MMR), and rabies, it has several drawbacks. A significant disadvantage is the time that it takes to develop a vaccine. Vaccines that are developed using chicken eggs can take upwards of six to 12 months for development, production, and release testing activities. This timeline would prove to be excessively long if a pandemic outbreak were to occur.5

Another concern regarding the production of vaccines in chicken eggs is that production capacity is limited to the number and availability of specific pathogen-free fertilized eggs and the finite capacity of current manufacturing facilities. For example, with the influenza vaccine, one egg is required for each dose of vaccine. Therefore, for a million doses, a million chicken eggs must be processed. This method is not ideal for rapid large-scale production scale-up requirements. The specific strain and species of the disease also can present challenges to the actual production of the vaccine in embryonated eggs. Certain virus strains may not replicate productively in an embryonic avian host, which can then require additional process optimization and production time. For example, the H5N1 strain of the avian influenza is generally deadly to chicken embryos and therefore, an alternative method must be employed for the production of the vaccine.6 In addition, even for avian flu strains that could be produced in chicken embryos, in the event of a pandemic, the availability of eggs would be severely impacted. Another disadvantage of producing vaccines in eggs is that people with allergies to eggs may react negatively to egg-based vaccines.

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