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| Fig.1 - Recombinant DNA |
Recombinant
DNA technology, in which a section of DNA from one species is inserted into the
DNA of another (see figure 1), is proving to be useful in the manufacture of
vaccines that contain only the desired antigen - usually one or several
proteins - without the need for attenuated toxins or modified versions of the
disease causing virus or bacterium. This results in the production of an immune
response without the risk of actual contraction of the original disease, and is
potentially more cost effective and commercially viable.
How Are Recombinant Vaccines Delivered?
Recombinant
vaccines can be delivered to recipient organisms via a live vector such as the Vaccinia
virus (which carries a gene for a rabies glycoprotein), or in the expressed
protein form as in Tickgard cattle vaccine or the Gardasil cervical cancer
vaccine. In such cases a purified protein preparation is usually injected into
the muscles.
To
produce such vaccines containing actual antigen proteins, the desired gene is
often inserted into bacteria or yeasts, which are cultured on a large scale.
The proteins produced from these transgenic
species are then incorporated into a vaccine preparation. Some
animal vaccines are actually now being trialled in the form of an oral vaccine
containing an antigenic protein which can be introduced in the animal’s feed.
How Are Recombinant Vaccines Made?
An
example of how the process works can be seen in the production of Tickgard
vaccine. Here, genes responsible for the manufacture of the gut protein Bm86 in
the cattle tick, Rhipicephalus microplus, are inserted into the DNA of
microbes. These microbes are cultured, and express the Bm86 protein on a large
scale. The protein can then be purified and injected into cattle, with the
result that their immune system will protect them against the Bm86 antigen
introduced in a real tick bite.
Current
research has found that, although the Bm86 gene can be adequately expressed in
recombinant E. coli bacteria and strains of the fungus Aspergillus, the yeast,
Pichia pastoris has proved to be the most successful at secreting the protein.
One reason for this is its rapid growth rate and its ability to grow on
inexpensive media.
Recombinant Vaccines Used by Humans
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| Fig.2 - Gardasil Vaccine |
Besides
Gardisal cervical cancer vaccine, one of the only other few recombinant
vaccines currently used in humans is the Hepatitis B Virus (HBV) vaccine, which
contains a surface protein from the hepatitis virus. This protein is produced
by recombinant yeast cells and then purified for injection. The HBV vaccine is
much safer to use than a weakened form of the actual virus, which, if it
reverts back to its original form, could cause liver cancer or hepatitis.
Another
recombinant vaccine that has been successfully trialled for human use is the
recombinant influenza vaccine, although it has not yet been produced on a
commercial basis. Feder, 2009,
in fact argues that the US should have had batches of this recombinant vaccine
prepared in advance during the swine flu (H1N1) outbreak in 2009, as it is fast
to produce and obviates the reliance on vaccines from overseas. Recombinant
influenza vaccines are composed of hemagglutinin, a protein present in various
strains of the influenza virus. This protein is expressed by recombinant cell
cultures and later purified to produce the vaccine.
Recombinant Vaccines For Animal Use
Several
commercially used recombinant vaccines used on animals employ a vector based
delivery system. These include the VRG vaccine, which protects animals against
rabies, and the Purevax recombinant feline leukaemia vaccine.
As
mentioned above,the VRG vaccine consists of a recombinant Vaccinia virus
that carries the gene for a rabies glycoprotein.The virus has been modified in
several ways, one of which involves the removal of the thymidine kinase gene,
making it safer to administer than in its original form. Studies have in fact
shown it has not caused any side effects in over 10 avian species and 35
mammalian species.
The
Purevax leukaemia vaccine contains a harmless recombinant canarypox virus that
incorporates the FeLV gene. This gene produces a protein identical to that
produced by the FeLV (feline leukaemia) virus, with the result that the cat's
immune response is triggered without the danger of the actual virus being
introduced. The canarypox virus is also used as a vector in dog and ferret
vaccines.
The Future of Recombinant Vaccines
Further
research is likely to increase the availability and effectiveness of
recombinant vaccines, resulting in safer preparations that are tailor made to
specific diseases in both animals and humans.Vaccines against non-infectious
diseases such as diabetes and for protection against parasitic organisms in
animals may also become a possibility. Methods of delivery will also undergo
improvement, especially in relation to orally introduced treatments.
References
Canales,
et.al., 2008, 'Expression of Recombinant Rhipicephalus (Boophilus)
microplus, R. annulatus and R. decoloratus Bm86 orthologs as secreted
proteins in Pichia pastoris', Biomedcentral.com, accessed 5/4/2010
Feder,
N., 2009, 'Recombinant Vaccine for Pandemic Flu: Why is it Not in Large Scale
Production?', Pogo.org, accessed 6/4/2010
World
Health Organisation, 2010, 'Recombinant Vaccines for Oral Immunisation of
Wildlife', Who.int, accessed 3/4/2010
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