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Cell wall structures which may be important for successful immunization with Salmonella-Shigella hybrid vaccines
C L Schultz1, B Kaufman, D Hamilton
1Department of Biologics Research, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
Abstract:
Three separate lots of S. typhi/S. sonnei hybrid (Ty/Shig) live oral vaccine strain 5076-1C were tested for efficacy in human volunteers challenged with virulent S. sonnei. Two lots (2 and 5) protected volunteers, a third lot (8) did not. The three lots were evaluated by immunological tests and electron microscopy. Lots 2 and 5, which protected, contained bacteria that reacted with anti-flagellar serum and had observable attached flagella and pili. Lot 8, which failed to protect, did not react with anti-flagellar serum, and had no observable pili. There was no correlation between vaccine efficacy and the reaction of IgG in patient's sera in western blot analysis. Surface structures on the Ty-Shig hybrid may be important for generating a protective immune response.
Insights
Efficacy of the S. typhi/S. sonnei hybrid (Ty/Shig) live oral vaccine strain 5076-1C varied between lots. Protected lots had observable flagella and pili, suggesting these surface structures are crucial for immune response.
Area of Science:
- Microbiology
- Vaccinology
- Immunology
Background:
- Shigellosis remains a significant global health concern, necessitating effective vaccines.
- The development of live oral vaccines, such as the S. typhi/S. sonnei hybrid (Ty/Shig) strain 5076-1C, offers a promising approach to combatting Shigella infections.
Purpose of the Study:
- To evaluate the efficacy of different lots of the Ty/Shig live oral vaccine strain 5076-1C in human volunteers.
- To identify potential correlates of protection for the Ty/Shig vaccine.
Main Methods:
- Human volunteers were challenged with virulent S. sonnei after vaccination with three separate lots of the Ty/Shig vaccine.
- Vaccine lots were analyzed using immunological tests and electron microscopy to assess bacterial surface structures.
Main Results:
- Two vaccine lots (2 and 5) demonstrated protective efficacy against S. sonnei challenge, while one lot (8) did not.
- Protected vaccine lots (2 and 5) exhibited reactivity with anti-flagellar serum and possessed observable flagella and pili.
- The non-protective lot (8) lacked observable pili and did not react with anti-flagellar serum.
Conclusions:
- The presence of flagella and pili on the Ty/Shig hybrid vaccine strain appears critical for inducing a protective immune response.
- Surface structures of the Ty/Shig vaccine are important factors influencing its efficacy.