Pox viruses as eukaryotic cloning and expression vectors: future medical and veterinary vaccines

It was proposed at the beginning of this article that the use of poxviruses as expression vectors provided a means of optimizing the conditions and prerequisites of vaccination and of elucidating a number of the associated problems. These advantages will now be summarized. Vaccinia virus recombinants carrying one or more multiple foreign genes have been shown to induce a sufficient immune response to that antigen in laboratory animals to protect against subsequent challenge by the infectious agent. In those animals tested the duration of immunity has been long-lasting with no apparent detrimental side-effects. Vaccinia virus is very stable in normal environmental situations and no cold-chain is required in the distribution network. There is no evidence for genetic instability of the vaccinia 'carrier' strain nor of loss of the inserted genetic elements. The vaccine is administered intradermally and it is proposed that one inoculation will be sufficient to induce immunity to multiple disease antigens; however, re-inoculation at a later time with the same or new antigenic determinants is not precluded. The efficiency of vaccinia virus as the vaccine strain used to eliminate the disease of smallpox with minimal side-effects is well documented. The recent studies described here on the development of vaccinia as a viral vector confer other advantages. Since the expression of the inserted genetic element is under vaccinia virus control, different levels of expression can be engineered by substituting the promoter sequence placed proximal to the insert. This leads to the possibility of high levels of expression when required for a single antigen or more modulated levels when multiple foreign antigens are expressed and 'genetic overload' could become a problem. Much work remains to be done on the body's immune response to this proposed genetic intrusion. The ability to insert large amounts of genetic information without disrupting virus replication and assembly indicates a great degree of flexibility in the genome strategy of the virus. This may indicate that the replication system can be further disrupted to eliminate or modify those sequences coding for virulence and wide host range to make the poxvirus vector as safe as possible for vaccine use. One of the reasons traditional vaccine strategy has failed for some virus groups is the degree of variability found in virus strains in nature. Influenza viruses are a good example, as are the bluetongue virus group, rotaviruses and bunyaviruses.(ABSTRACT TRUNCATED AT 400 WORDS)