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Infection and Immunity, February 1999, p. 782-788, Vol. 67, No. 2
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Strategy for Cross-Protection among Shigella flexneri Serotypes

Fernando R. Noriega,* Fang Ming Liao, David R. Maneval, Shuxun Ren, Samuel B. Formal, and Myron M. Levine

Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland 21201

Received 31 July 1998/Returned for modification 1 October 1998/Accepted 17 November 1998

Based upon the lipopolysaccharide (LPS) structure and antigenicity of Shigella group B, a strategy for broad cross-protection against 14 Shigella flexneri serotypes was designed. This strategy involves the use of two S. flexneri serotypes (2a and 3a), which together bear the all of the major antigenic 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 sen) and S. flexneri 3a strain CVD 1211 (Delta guaB-A Delta virG Delta sen). Guinea pigs were immunized with an equal mixture of these strains and later challenged (Sereny test) with a wild-type S. flexneri serotype 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 produced serum and mucosal antibodies that cross-reacted with all the S. flexneri serotypes tested (except of S. flexneri serotype 6) as assessed by enzyme-linked immunosorbent assay, immunoblotting, and slide agglutination. Furthermore, the combination vaccine conferred significant protection against challenge with S. flexneri serotypes 1b, 2b, 5b, and Y but not with serotypes 1a, 4b, or (as predicted) 6.

* Corresponding author. Present address: Clinical Development, Pasteur Mérieux Connaught, Discovery Drive, Swiftwater, PA 18370-0187. Phone: (717) 839-6188. Fax: (717) 839-0934. E-mail: fnoriega{at}us.pmc-vacc.com.

Infection and Immunity, February 1999, p. 782-788, Vol. 67, No. 2
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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Copyright © 1999 by the American Society for Microbiology. All rights reserved.