bacteria autolyze as a result of the accumulation of intermediate products 
of metabolism that cannot be further processed. The best examples of this 
prototype bacterial vaccine are the attenuated Sal monel 1 a t yph i and 
Sal monel 1 a t yph i mur i urn gal E mutant strains that have a complete lack of 
the enzyme UDF'-gal ac t ose-4-ep i rner ase . Ty21a, a gal E mutant of S. t yph i 
isolated in the early 1970s after chemical mutagenesis, has shown the 
advantages of this variety of attenuation. Grown in the presence of 
galactose, which results in the production of smooth 1 i popol ysacchar i de 0 
antigen, this vaccine strain is safe, immunogenic and protective but is 
also rarely recoverable from coprocultures. Large-scale field trials in 
Egypt and Chile, involving more than 600,000 schoolchildren, have 
demonstrated the safety and efficacy of the Ty21a live oral typhoid 
vaccine. Ty21a is presently licensed in many countries of Europe, Latin 
America, Asia and Africa and is expected to be licensed shortly in the 
U.S.A. Following ingestion of doses of this live oral vaccine containing 
circa 1—3 billion viable organisms, the vaccine is not recoverable from 
copr ocul tur es . This is a consequence of the method of attenuation. 
Gal E mutants of S. typhi . S. t yph i mur i urn . and Sh i gel 1 a f 1 exner i have 
been prepared by recombinant DNA techniques, by means of deletions of the 
gal E gene. These vaccines have distinct potential advantages over 
chemically mutagenized strains and clinical evaluations of the safety and 
i mmunogeni c i ty of these vaccine candidates should therefore be expedited. 
Self-destructing, non-t r ansmi ssi b 1 e vaccine strains of the above 
variety should be exempt from the guidelines. It should be recommended, 
however, that vaccine candidates of this variety should contain a marker 
such as a resistance to Hg++ ions, a stable biochemical marker, or 
resistance to a clinically irrelevant antibiotic, to allow ready 
Recombinant DNA Research, Volume 1 1 
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