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Live Virus and Bacteria. Another delivery system that is attracting attention is the use of recombinant technology to create yeast viruses and bacteria that express antigen. This has already been done with hepatitis B, removing DNA from the pathogen and introducing it into a vector that then produces the immunizing antigen. Some potential vectors can be administered intranasally, orally, and/or rectally. It may also be possible to induce more than one antigen in a single vector, and the cost of producing these vaccines is fairly low.

Among the bacteria being explored as vectors are E. coli, BCG (attenuated Mycobacterium bovis), Shigella, and lactobacilli. These microbial vectors are immunogenic by themselves, and consequently they cannot be used for a second immunization. Lactobacilli show particular promise because children are usually colonized at an early age, so the immune response is minimal. There is some risk of contaminating the environment with recombinant bacteria.

Viruses may have many advantages, including better control over the conformation and glycosylation of the expressed antigen. Promising vectors include poliovirus, influenza, canarypox, and rhinovirus. Both influenza and canarypox have been used to express HIV antigens in human experiments.

These vectors have disadvantages that must be overcome. For example, the dominant response is always to the vector rather than the antigen. The major problem for immunology, however, is that the level of expression of the desired antigen is extremely low; this might be overcome by inserting multiple copies of the gene. In addition, bacterial vectors do not always produce antigen with the proper secondary and tertiary structure.

Plants. Several groups are looking at plants as possible delivery systems. The tobacco plant in particular is called “the white mouse of botany” because its genes are well known and easy to manipulate using the tobacco mosaic virus, which can infect 400 other plants. Researchers in England have already succeeded in producing hepatitis B antigens in tobacco leaves. Other plants that are being considered as delivery systems include potato, beet, rice, lettuce, tomato, and bananas. Bananas would be particularly attractive in tropical areas, but the intended antigen is produced at low levels—100 micrograms of hepatitis B protein per banana, rather than the 10 milligrams researchers had hoped for.

Plants can also be used to produce specific antigens, including secretory IgA containing the secretory element. This has been done by introducing genes for the heavy chains of IgA into tobacco, and could conceivably be done with edible plants as well. The result could be an edible delivery system for highly specific secretory IgA antibodies against rotavirus, salmonella, etc., as well as antigens. This could become one of the vaccines of the future.

DNA Immunization. DNA vaccines are covered in greater detail in the following summary. However, this is a difficult route of immunization because of generally poor reproducibility and low uptake of DNA. It may be possible to increase uptake using microspheres or other systems. It is unclear at present



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