Antiviral inducing properties of staphylococcal enterotoxin mimetic peptides (VAC9P.1065)

Abstract

Abstract Superantigens, like the staphylococcal enterotoxins, activate vast numbers of T-cells to produce large amounts of cytokines, including interferon-gamma (IFN-γ), and eventually cause these cells to undergo apoptosis. The objective of this research was to design mimetic peptides of staphylococcal enterotoxins that are not toxic to cells, but can produce antiviral activity in cells via production of IFN-γ. Based on the amino acid sequences of staphylococcal enterotoxins (SE) A, B, C, and toxic shock syndrome toxin, peptides were designed to mimic the antigenic sites of these superantigens. Whole protein superantigens (SEA) at concentrations ranging from 1.0 to 10.0ng/mL stimulated T-cell proliferation and induced IFN-γ production. Superantigen concentrations at or above 100ng/mL showed cellular toxicity. Of the eight mimetic peptides tested, SEA 3 was the only peptide that induced IFN-γ production, as determined by the IFN-γ ELISA kit, in HPBMC but did not induce cellular proliferation. SEA1, SEA2, and TSST peptides induced cellular proliferation but no IFN-γ stimulation. The peptides showed no toxicity directly on HeLa cells or HPBMC at 100 ug/mL or lower. Cell supernatant from the SEA3 peptide treated HPBMC also had antiviral activity against vesicular stomatitis virus. Thus, this study showed that mimetic peptides of superantigens could be developed that can induce T-cells to produce IFN-γ without the cellular toxicity associated with superantigens.