O-Specific Side-Chain Toxin-Protein Conjugates as Parenteral Vaccines for the Prevention of Shigellosis and Related Diseases

Only indirect evidence has been cited to document that lipopolysaccharide-mediated virulence at the bacterial level and serum antibodies to the o-specific side chain of the lipopolysaccharide molecule may prevent shigellosis. Our proposed use of the B subunit of Shiga toxin as a carrier protein is based upon evidence (even more indirect) that serum antitoxin may reduce the severity of dysentery and diarrhea. Because animal models of disease may provide information inap-plicable to the prediction of vaccine-induced protective immunity, we suggest that clinical trials in the population at risk should bestarted after successful completion of the safety and immunoge-nicity phases of vaccine development in laboratory animals and in the target population. Clinical studies of shigella vaccines are difficult because of the many causes of dysentery in a population with a high rate of intestinal disease. The component(s) of shigellae (and related bacteria) and of the host immune systemthat confer protection against en-teric diseasescausedbythesemicroorganisms remainunclear. That prevention is a worthwhileobjective in both developing and industrialized nations is clear from the high frequency