vaccine genome. 
5) Vaccine Strains Expressing CRM Toxoids 
Another approach is to modify the toxin genes of organisms in which 
toxin is the critical virulence property and where antitoxin is important 
in protection so that the mutant elaborates a biologically inactive albeit 
immunogenic toxoid molecule (so-called cross-reacting molecule or CRM). 
Such mutants should have stable markers and should ideally be rec A minus 
strains or their equivalent. 
6) Bacteria with Plasmids Having Deletions of Critical Virulence Genes 
For some bacteria the critical virulence genes are plasmid-encoded and 
often two distinct genes (for example encoding ST and colonization 
fimbriae) are adjacent. Vaccine strains containing plasmids having 
deletions of critical virulence genes should also be exempt from the 
gui del i nes. 
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