Cross-reactivity of Shigella flexneri serotype 2a O antigen antibodies following immunization or infection

To study the cross-reactivity pattern of Shigella flexneri 2a O-antigen antibodies, sera from humans and monkeys challenged with S. flexneri 2a, and from humans and guinea pigs immunized with a recombinant vaccine expressing serotype 2a O-antigen, were tested against a panel of lipopolysaccharide extracted from heterologous S. flexneri. Sera from the two groups of humans, who were volunteers in either a clinical challenge or vaccination study, showed similar patterns: cross-reactivity was more often seen with IgA antibodies, and these were mostly cross-reactive with serotype 2b, which shares the type II antigen, and serotypes 1a, 5a, and Y, which share 4 or 3, 4 group antigen, with 2a. The majority of sera from immunized guinea pigs showed both IgG and IgA cross-reactivity with 1a, 5a, and Y, but not 2b. The majority of sera from challenged monkeys showed cross-reactivity with almost all flexneri serotypes tested, with 1a, 2b, and Y being recognized most often, and the cross-reactive antibodies were more often IgG than IgA. These results show that either immunization or challenge with the 2a serotype induces cross-reactive antibodies which recognize similar subsets of heterologous serotypes, and suggest that it may be possible to design multivalent vaccines against S. flexneri.