Immunity in {Shigellosis}. {I}. {Response} of {Man} to {Attenuated} {Strains} of {Shigella}

Four attenuated strains of Shigella flexneri 2a have been tested for stability and safety as vaccines in man. One strain, a Shigella-Escherichia coli hybrid, was virulent for man in doses of 108 cells, while a mutant strain reverted to virulence when 1010 cells were administered orally. Two vaccine strains, a Shigella mutant E. coli hybrid and a streptomycin-dependent mutant, were safely given to adult males in doses of 5–10 × 1010 cells. Pretreatment with sodium bicarbonate was essential for the assurance of intestinal transit of viable vaccine organisms, and less than one-third of those vaccinated developed rises in humoral antibody. Streptomycin-independent revertants could be recovered only rarely in vivo when the streptomicin-dependent mutant was used, and one revertant found was avirulent. These studies have outlined the important biologic requirements of potential live oral shigella vaccines. Strains must not penetrate the intestinal mucosa and must be stable without reverting to virulence at levels of dosage used.