Biotechnology and Bioinformatics (1+1)

4.3.9. Gene tically modified live vaccines

Pathogens with defined genetic manipulations or microbial vector s carrying the gene coding for immunogenic protein can be used as live vaccines. Live vaccines replicate inside the recipient host resembling the natural infection and thus induce strong immunity. This kind of vaccine is reported to be highly immunogenic than the non-replicating vaccine products.

Selection of a stable non-pathogenic mutant usable as live vaccine is a complex process in the sense that it involves tedious procedure of growing viruses in different culture conditions or introducing targeted mutations, followed by in vivo and in vitro assays.

Some important methods of selection of attenuated mutants are,

• adaptation to heterologous cell line,
• adaptation to elevated temperature and
• selection of neutralizing monoclonal antibody escape mutants. The rationale behind selection of strain s adjusted to such extreme conditions is that these strains are believed to be altered genetically hence resulting alteration of their virulence. Nucleotide sequence analysis of such strains can confirm the position of mutation.
• Further, invivo and in vitro analysis can reveal their phenotypic variation hence aiding in election of such strains as candidates for live vaccine.
• Defined genetic alterations resulting in mutants with desired phenotype can be achieved using site directed mutagenesis technique also.
• Live vaccines have been used against some of the fish bacterial pathogens such as A. salmonicida and A. hydrophila.
• Several techniques such as homologous recombination,chemical mutagenesis and transpos on mutagenesis are used to produce mutant bacteria those are a virulant and capable of being used as live vaccines.