Quality assessment of DNA vaccines: hepatitis-B vaccine.

Vaccines manufactured following "classical" methods contain inactivated or infectious but attenuated viruses or bacteria. In some instances, the inactivated agents are purified. In other cases, the vaccines contain protein subunits or practically pure polysaccharides. It is generally accepted that the final product cannot be completely characterised and that therefore extensive "in-process" controls are necessary to prove the consistent quality of such vaccines. Control tests are carried out on the substrate, the pooled bulk vaccine and on the final containers. Vaccines produced by recombinant DNA techniques consist of pure proteins. The production is carried out by the multiplication of the "working seed" under well-defined standardised conditions followed by clarification, extraction, purification, formulation. "In-process" controls are incorporated at each step and specifications for acceptance are formulated. The biological methods used for the classical vaccines are completed by physicochemical and immunological determinations of antigen content, identity and purity for the "new generation" products. The requirements for the manufacturers are based on the documents issued by the World Health Organisation and by the national control authorities. The marketing of vaccines is based on a lot by lot release procedure, whereby each lot is tested by the manufacturer and the national control authority before use. Hepatitis-B vaccine, derived from transformed yeast cells, is the first and sole vaccine which has obtained a world-wide license. The quality assessment of this vaccine has been achieved following the requirements for the new generation of biomolecules. It is an example for future vaccines.

The protection of chimpanzees against hepatitis B viral infection using a recombinant yeast-derived hepatitis B surface antigen.

In order to determine the efficacy of the SmithKline Biologicals recombinant DNA yeast-derived hepatitis B vaccine in inducing protection against hepatitis B infection, two chimpanzees were injected intramuscularly with 20 micrograms according to a 0-, 1-, and 2-month schedule. After the second dose, the vaccinated animals already showed a significant antibody response. One month after the last injection, the animals were challenged with hepatitis B virus. The vaccinated animals were protected while the two unvaccinated controls showed all signs of hepatitis B infection. One year after vaccination, antibodies remained high and were comparable with levels produced by plasma-derived vaccines.

Specifications and quality control of a yeast-derived hepatitis B vaccine.

It is essential that the new generation of recombinant DNA yeast-derived hepatitis B vaccines be prepared according to techniques which are adequately controlled to ensure their safety and efficacy. Various national and supra-national authorities have already issued guidelines for specifications and standardization of such products. Based on these guidelines, the potential hazards, and the state-of-the-art technology, SmithKline Biologicals has developed specifications and analytical methods to cover all aspects of the quality assessment of its recombinant hepatitis B vaccine, Engerix-B. This includes adequate 'in-process' tests to guarantee the optimal reproducibility and standardization of the entire production process as well as methods to study the characteristics and identity of the expressed antigen protein. Finally, specifications and methods of analysis necessary to control the purified bulk product and vaccine in its final container ensure the purity, safety, identity, potency, and stability of each production lot.