Abstract
Attenuated strains of Salmonella have been used effectively as vaccines against typhoid fever. We have investigated the use of such strains to deliver cloned antiphagocytic virulence determinants of unrelated bacteria. The aroA strain of S. typhimurium SL3261 was transformed with a low-copy plasmid vector pMK207, which contains the cloned gene spm5 encoding streptococcal M protein, the major virulence factor of these organisms. The transformed SL3261 expressed type 5 M protein in the cytoplasmic fraction, and when fed orally to BALB/c mice, evoked both serum and salivary IgA, IgG, and IgM antibodies directed against type 5 M protein. The orally immunized mice were completely protected against both intranasal and intraperitoneal challenge infections with virulent S. typhimurium SL1344 or M5 streptococci. These studies provide evidence that an attenuated strain of Salmonella can be used effectively as a general vaccine vehicle to deliver antiphagocytic virulence determinants of unrelated bacteria.
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Selected References
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- Beachey E. H., Gras-Masse H., Tarter A., Jolivet M., Audibert F., Chedid L., Seyer J. M. Opsonic antibodies evoked by hybrid peptide copies of types 5 and 24 streptococcal M proteins synthesized in tandem. J Exp Med. 1986 Jun 1;163(6):1451–1458. doi: 10.1084/jem.163.6.1451. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beachey E. H., Seyer J. M., Dale J. B. Protective immunogenicity and T lymphocyte specificity of a trivalent hybrid peptide containing NH2-terminal sequences of types 5, 6, and 24 M proteins synthesized in tandem. J Exp Med. 1987 Sep 1;166(3):647–656. doi: 10.1084/jem.166.3.647. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beachey E. H., Seyer J. M., Kang A. H. Primary structure of protective antigens of type 24 streptococcal M protein. J Biol Chem. 1980 Jul 10;255(13):6284–6289. [PubMed] [Google Scholar]
- Bullas L. R., Ryu J. I. Salmonella typhimurium LT2 strains which are r- m+ for all three chromosomally located systems of DNA restriction and modification. J Bacteriol. 1983 Oct;156(1):471–474. doi: 10.1128/jb.156.1.471-474.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dale J. B., Beachey E. H. Multiple, heart-cross-reactive epitopes of streptococcal M proteins. J Exp Med. 1985 Jan 1;161(1):113–122. doi: 10.1084/jem.161.1.113. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dale J. B., Beachey E. H. Protective antigenic determinant of streptococcal M protein shared with sarcolemmal membrane protein of human heart. J Exp Med. 1982 Oct 1;156(4):1165–1176. doi: 10.1084/jem.156.4.1165. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fischetti V. A., Jones K. F., Manjula B. N., Scott J. R. Streptococcal M6 protein expressed in Escherichia coli. Localization, purification, and comparison with streptococcal-derived M protein. J Exp Med. 1984 Apr 1;159(4):1083–1095. doi: 10.1084/jem.159.4.1083. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoiseth S. K., Stocker B. A. Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines. Nature. 1981 May 21;291(5812):238–239. doi: 10.1038/291238a0. [DOI] [PubMed] [Google Scholar]
- KAPLAN M. H., MEYESERIAN M. An immunological cross-reaction between group-A streptococcal cells and human heart tissue. Lancet. 1962 Apr 7;1(7232):706–710. doi: 10.1016/s0140-6736(62)91653-7. [DOI] [PubMed] [Google Scholar]
- Kehoe M. A., Poirier T. P., Beachey E. H., Timmis K. N. Cloning and genetic analysis of serotype 5 M protein determinant of group A streptococci: evidence for multiple copies of the M5 determinant in the Streptococcus pyogenes genome. Infect Immun. 1985 Apr;48(1):190–197. doi: 10.1128/iai.48.1.190-197.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LANCEFIELD R. C. Current knowledge of type-specific M antigens of group A streptococci. J Immunol. 1962 Sep;89:307–313. [PubMed] [Google Scholar]
- Lederberg E. M., Cohen S. N. Transformation of Salmonella typhimurium by plasmid deoxyribonucleic acid. J Bacteriol. 1974 Sep;119(3):1072–1074. doi: 10.1128/jb.119.3.1072-1074.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Phillips G. N., Jr, Flicker P. F., Cohen C., Manjula B. N., Fischetti V. A. Streptococcal M protein: alpha-helical coiled-coil structure and arrangement on the cell surface. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4689–4693. doi: 10.1073/pnas.78.8.4689. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Poirier T. P., Kehoe M. A., Dale J. B., Timmis K. N., Beachey E. H. Expression of protective and cardiac tissue cross-reactive epitopes of type 5 streptococcal M protein in Escherichia coli. Infect Immun. 1985 Apr;48(1):198–203. doi: 10.1128/iai.48.1.198-203.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swanson J., Hsu K. C., Gotschlich E. C. Electron microscopic studies on streptococci. I. M antigen. J Exp Med. 1969 Nov 1;130(5):1063–1091. doi: 10.1084/jem.130.5.1063. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zabriskie J. B., Freimer E. H. An immunological relationship between the group. A streptococcus and mammalian muscle. J Exp Med. 1966 Oct 1;124(4):661–678. doi: 10.1084/jem.124.4.661. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van de Rijn I., Zabriskie J. B., McCarty M. Group A streptococcal antigens cross-reactive with myocardium. Purification of heart-reactive antibody and isolation and characterization of the streptococcal antigen. J Exp Med. 1977 Aug 1;146(2):579–599. doi: 10.1084/jem.146.2.579. [DOI] [PMC free article] [PubMed] [Google Scholar]