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Publication : Biological activity of toxic shock syndrome toxin 1 and a site-directed mutant, H135A, in a lipopolysaccharide-potentiated mouse lethality model.

First Author  Stiles BG Year  1995
Journal  Infect Immun Volume  63
Issue  4 Pages  1229-34
PubMed ID  7890377 Mgi Jnum  J:23917
Mgi Id  MGI:71654 Doi  10.1128/iai.63.4.1229-1234.1995
Citation  Stiles BG, et al. (1995) Biological activity of toxic shock syndrome toxin 1 and a site-directed mutant, H135A, in a lipopolysaccharide-potentiated mouse lethality model. Infect Immun 63(4):1229-34
abstractText  A recombinant of toxic shock syndrome toxin 1 (TSST-1) which contains a single histidine-to-alanine mutation at residue 135 (H135A) was analyzed for toxicity and vaccine potential in a lipopolysaccharide (LPS)-potentiated mouse lethality model. The 50% lethal dose (LD50) of TSST-1 in BALB/c mice was 47.2 micrograms/kg, but H135A was not lethal when tested at a dose equivalent to 10 LD50s of TSST-1. Levels of tumor necrosis factor (TNF) and gamma interferon (IFN-gamma) in serum were, respectively, 10- and 50-fold higher in LPS-potentiated mice injected with 15 LD50s of TSST-1 than in mice given H135A. Mice injected with only TSST-1 did not have elevated levels of TNF or IFN-gamma in serum, while H135A plus LPS or LPS alone elicited identical, yet very low, levels of TNF and IFN-gamma. An enzyme-linked immunosorbent assay of H135A and TSST-1 with anti-TSST-1 serum yielded very similar dose-response curves, which strongly suggests that H135A serologically and conformationally resembles the native toxin. Mice immunized with H135A developed antibodies that recognized TSST-1 in an enzyme-linked immunosorbent assay and afforded protection against a 15-LD50 challenge of TSST-1 plus LPS. The pooled sera of mice immunized with either TSST-1 or H135A also prevented lymphocyte proliferation due to TSST-1.
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