Journal article
Toxoids of Streptococcal Pyrogenic Exotoxin A Are Protective in Rabbit Models of Streptococcal Toxic Shock Syndrome
Infection and immunity, Vol.68(9), pp.5011-5017
09/2000
DOI: 10.1128/IAI.68.9.5011-5017.2000
PMCID: PMC101724
PMID: 10948118
Abstract
Streptococcal pyrogenic exotoxins (SPEs) are superantigens that have been implicated in causing streptococcal toxic shock syndrome (STSS). Most notably, SPE serotype A is made by nearly all M-protein serotype 1 and 3 streptococci, the M types most associated with the illness (these strains contain one or more other SPEs, and those proteins are likely also to contribute to disease). We have prepared double-, triple-, and hexa-amino-acid mutants of SPE A by PCR and other mutagenesis procedures. The sites chosen for mutation were solvent-exposed residues thought to be important for T-cell receptor (TCR) or major histocompatibility complex (MHC) class II interaction. These mutants were nonsuperantigenic for human peripheral blood mononuclear cells and rabbit and mouse splenocytes and were nonlethal in two rabbit models of STSS. In addition, these mutants stimulated protective antibody responses. Interestingly, mutants that altered toxin binding to MHC class II were more immunogenic than mutants altering TCR binding. Collectively, these studies indicate that multiple-site mutants of SPE A are toxoids that may have use in protecting against the toxin's effects in STSS.
Details
- Title: Subtitle
- Toxoids of Streptococcal Pyrogenic Exotoxin A Are Protective in Rabbit Models of Streptococcal Toxic Shock Syndrome
- Creators
- Manuela Roggiani - University of Minnesota, Minneapolis, Minnesota 55455, and Wyeth Lederle Vaccines, West Henrietta, New York 14586Jennifer A Stoehr - University of Minnesota, Minneapolis, Minnesota 55455, and Wyeth Lederle Vaccines, West Henrietta, New York 14586Stephen B Olmsted - University of Minnesota, Minneapolis, Minnesota 55455, and Wyeth Lederle Vaccines, West Henrietta, New York 14586Yury V Matsuka - University of Minnesota, Minneapolis, Minnesota 55455, and Wyeth Lederle Vaccines, West Henrietta, New York 14586Subramonia Pillai - University of Minnesota, Minneapolis, Minnesota 55455, and Wyeth Lederle Vaccines, West Henrietta, New York 14586Douglas H Ohlendorf - University of Minnesota, Minneapolis, Minnesota 55455, and Wyeth Lederle Vaccines, West Henrietta, New York 14586Patrick M Schlievert - University of Minnesota, Minneapolis, Minnesota 55455, and Wyeth Lederle Vaccines, West Henrietta, New York 14586
- Resource Type
- Journal article
- Publication Details
- Infection and immunity, Vol.68(9), pp.5011-5017
- DOI
- 10.1128/IAI.68.9.5011-5017.2000
- PMID
- 10948118
- PMCID
- PMC101724
- NLM abbreviation
- Infect Immun
- ISSN
- 0019-9567
- eISSN
- 1098-5522
- Publisher
- American Society for Microbiology
- Language
- English
- Date published
- 09/2000
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984001114002771
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