AROD DELETION ATTENUATES SHIGELLA-FLEXNERI STRAIN 2457T AND MAKES IT A SAFE AND EFFICACIOUS ORAL VACCINE IN MONKEYS

The aromatic-dependent live Shigella flexneri 2a vaccine strain SFL107 0, with a deleted aroD gene, had a much reduced intracellular growth i n HeLa cells compared with its parent strain S. flexneri 2457T. S. fle xneri SFL]070 gave no adverse effects in eight Macaca fascicularis mon keys orally vaccinated with four doses of 1 x 10(11) live bacteria wit hin a 5-week period, whereas S. flexneri 2457T caused dysentery in all eight non-vaccinated monkeys. Thus the aromatic dependency rendered S . flexneri SFL1070 significantly attenuated (p = 0.00008). Significant intestinal S. flexneri lipopolysaccharide (LPS)-specific sIgA respons es were seen in seven of eight vaccinated monkeys (p < 0.01) after fou r doses with SFL]070. However, serum IgG or IgA responses to various S . flexneri LPS antigens and the invasion plasmid antigens (Ipa-s) were seen in only four of eight vaccinated monkeys. The serum IgG titre in creases against S. flexneri Y and 2a LPS reached significant levels (p less-than-or-equal-to 0.05). All but one of the vaccinated monkeys we re protected against oral challenge with 1 x 10(10) or 1 x 10(11) live S. flexneri 2457T given 2 weeks after the last vaccination. The prote ction was highly significant (p = 0.0007) as all non-vaccinated monkey s challenged with equal doses of strain 2457T developed dysentery. Thr ee of them succumbed. Challenge infection of vaccinated monkeys elicit ed serum IgA and IgG responses to the homologous S. flexneri 2a LPS in three monkeys each (0.005 less-than-or-equal-to p less-than-or-equal- to 0.025). Serum IgA and IgG responses to the Ipa-s were seen in five and four monkeys each (0.01 < p less-than-or-equal-to 0.05). No signif icant intestinal antibody responses were seen in this group of vaccina ted and challenged monkeys.