Strategy for cross-protection among Shigella flexneri serotypes

Based upon the lipopolysaccharide (LPS) structure and antigenicity of Shige lla group B, a strategy for broad cross-protection against 14 Shigella flex neri serotypes was designed. This strategy involves the use of two S. flexn eri serotypes (2a and 3a), which together bear the all of the major antigen ic group factors of this group. The novel attenuated strains used in these studies were S. flexneri 2a strain CVD 1207 (Delta guaB-A Delta virG Delta set1 Delta set1) and S. flexneri 3a strain CVD 1211 (Delta guaB-A Delta vir G Delta sen). Guinea pigs were immunized with an equal mixture of these str ains and later challenged (Sereny test) with a wild-type S. flexneri seroty pe 1a, 1b, 2b, 4b, 5b, Y, or 6 strain of demonstrated virulence in the same model. Guinea pigs that were immunized with these two vaccine strains prod uced serum and mucosal antibodies that cross-reacted with all the S. flexne ri serotypes tested (except of S. flexneri serotype 6) as assessed by enzym e-linked immunosorbent assay, immunoblotting, and slide agglutination, Furt hermore, the combination vaccine conferred significant protection against c hallenge with S. flexneri serotypes 1b, 2b, 5b, and Y but not with serotype s la, 4b, or las predicted) 6.