Vaccination consists of stimulating the immune system in a specific way to prevent or ameliorate diseases caused by infectious agents. Two different approaches have been used to induce protective immune responses: one utilizes the administration of antigenic inert substances (a structural component of the whole inactivated microbe) and the other is based on the use of highly attenuated infectious microorganisms which, upon administration, replicate within the host without causing disease, thus priming the immune system in the same manner as natural infection.
Recently, a radically new approach to vaccination has been developed which involves the direct injection of DNA sequences of protective antigen(s). The direct injection of genetic material into a living host causes some cells to produce the immunogenic protein resulting in the stimulation of an immune response to the pathogenic microorganism. This approach offers a number of potential advantages over traditional vaccines, including the stimulation of both B- and T-cell responses, improved vaccine stability, the absence of any infectious agent, and the relative ease of large-scale manufacture. The proof of concept of this approach has been established in many animal models to a variety of infectious agents, including influenza virus, hepatitis B virus, human immunodeficiency virus, rabies virus, lymphocytic choriomeningitis virus, malaria and mycoplasmas. In addition, in some cases, this vaccination approach has resulted in protection from disease. Nevertheless, many issues regarding efficacy and safety aspects of DNA vaccines need to be addressed before they can be approved for routine use in humans.
A number of technologies are also being developed to improve the delivery of DNA vaccines and/or to enhance the immune response induced (e.g. adjuvants). It is likely that the first DNA vaccine to be licensed for human use will be based on bacterial plasmids.
DNA Vaccine Standardization
WHO guidance on the quality and nonclinical safety evaluation of DNA vaccines was adopted by the Expert Committee for Biological Standardization (ECBS) in 2005. This document was formulated to provide national regulatory authorities and vaccine manufacturers a scientifically sound basis for the production and control of DNA vaccines intended for use in humans, and to assure their consistent safety and efficacy provide information. The section on nonclinical development was drawn up in response to the use of different experimental approaches to enhancing the efficacy of DNA vaccines which may raise specific safety concerns. WHO has developed guidelines to ensure that appropriate production methods and quality control tests are used for the manufacture of plasmid DNA vaccines. It is recognized that the development and application of nucleic acid vaccines are evolving rapidly, and that these guidelines will need to be revised and expanded in the future. Until that time, the control of nucleic acid vaccines should be approached in a flexible manner so that experience can be gained in their production and use.