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Recombinant Virus as Vaccine

	Recombinant Virus as Vaccine Live vaccines evoke the most effective immunity and are the cheapest to produce but in practice are very difficult to make. The idea of inserting the gene for a foreign neutralisation antigen into a pre-existing live vaccine So that it is expressed naturally as the virus multiplies, is indeed attractive. This has already been achieved experimentally for antigens of influenza, rabies, herpes simplex type I and hepatitis B viruses using vaccinia virus as the live vaccine. The virus is administered intradermally by scratching the skin.
The virus multiplies .at that site causing a reaction about the size of a small boil and stimulates both antibody and cell mediated immunity to viral antigens i.e. to those viruses whose genes have been cloned to make recombinant vaccinia virus. Thus vaccinating with a recombinant vaccinia virus having cloned haemagglutinin gene for, say influenza virus will protect against influenza virus antigens. There is inserted a cloned gene into a plasmid under the control of the promoter of the vaccinia Thymidine kinase (TK) gene. Upon transfection into vaccinia virus infected cells, recombination takes place because of the homologus TK sequences which both possess.
The TK gene is inactivated by insertion of the plasmid which means that recombinants can be selected because they are unable to utilise (and hence be inhibited by) the DNA synthesis inhibitor bromodeoxyuridine. Consequently only recombinant virus produces plaques. Animals infected with recombinant vaccinia carrying genes for hepatitis B S-antigen or influenza virus haemagglutinin respond with excellent antibody and cell mediated immune responses. So vaccines of this type are an exciting prospect.
The original virus vaccine, obtained- from fluid which exuded from localised intradermal infections of sheep, costs only $ O.31 per dose compared with $ 1.00 for live polio virus vaccine or $ 100 for current killed hepatitis B virus vaccine. A recombinant vaccinia virus vaccine would be produced in tissue culture and would cost about the same as the polio virus vaccine. We do not know yet as how effective and long lived could be anti vaccinial immunity. The interesting point is that the vaccinia genome can accommodate around 25 kilobases of DNA without losing infectivity. This means that the recombinant virus could express 10 to 20 foreign antigens and serve as a one-off polyvalent spectrum of virus diseases.

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