Surface-displayed viral antigens on Salmonella carrier vaccine

Abstract

We have developed a recombinant live oral vaccine using the ice-nucleation protein (Inp) from Pseudomonas syringae to display viral antigens on the surface of Salmonella spp. Fusion proteins containing viral antigens were expressed in the oral vaccine strain, Salmonella typhi Ty21a. Surface localization was verified by immunoblotting and fluorescence-activated cell sorting. The immunogenicity of surface-displayed viral antigens on the recombinant live vaccine strain was assessed in mice inoculated intranasally and intraperitoneally. Inoculation resulted in significantly higher serum antibody level than those induced by viral antigens expressed intracellularly. Thus, this multivalent mucosal live vaccine may provide an effective means for inducing mucosal or systemic immune responses against multiple viral antigens.

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Figure 1: Expression and localization of fusion proteins as shown by western blot with anti-HBsAg antibody (A and B, strips a-c) and anti-HCV core monoclonal antibody (B, strip d).
Figure 2
Figure 3: Serum anti-HBsAg IgG titers in mice in preimmune sera (0) or following one (a) or two (b) immunizations of recombinant S. typhi Ty21a cells harboring surface display plasmids (white bars, pKInc; diagonally hatched bars, pKInH; black bars, pKInHc; gray bars, pKIncH; horizontally hatched bars, pKInHcC).
Figure 4: Serum anti-HCV core IgG titers in mice inoculated with S. typhi Ty21a harboring the plasmid pKInHcC once (A) or twice (B).
Figure 5

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Acknowledgements

This work was supported in part by grant NRI 2000 from MOST (Ministry of Science and Technology) and grant BSKP1011 from KRIBB (Korea Research Institute of Bioscience and Biotechnology) of Korea. We thank Dr. S.A. Shin, Dr. H.C. Jung, and Dr. M.H. Sung for technical help and continuous encouragement during this work, and Dr. K. Shimotohno (National Cancer Center Research Institute, Japan) for a generous gift of p740 cDNA plasmid.

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Correspondence to Chul-Joong Kim.

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Lee, J., Shin, K., Pan, J. et al. Surface-displayed viral antigens on Salmonella carrier vaccine. Nat Biotechnol 18, 645–648 (2000). https://doi.org/10.1038/76494

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