Immunization with superantigen-derived oligopeptides protect against S. aureus bacteremia (VAC8P.1058)

Abstract

Abstract Staphylococcal superantigens are exotoxins that play a major role in disease pathogenesis. Using a T cell epitope prediction tool from the Immune Epitope Database Analysis Resource (IEDB) site, sequences within staphylococcal enterotoxin A and B (SEA, SEB) and Toxic Shock Syndrome Toxin with high affinity towards H2-Iab were identified and oligopeptides SEA_aa116-128, SEB_aa16-28 and TSST-1_aa212-224 were generated. C57BL/6 mice were immunized with a cocktail of oligopeptides or whole toxins in Al(OH)3. Serum samples from peptide-immunized mice tested positive towards individual peptides and whole toxins, however, samples from mice immunized with whole toxins did not bind to any of the peptides. To determine peptide-specific T cell response primed CD4 T cells isolated from spleens and total LNs of immunized mice were co-cultured with peptide-pulsed BMDCs and cytokine response was evaluated. Only cells of peptide-immunized mice resulted in elevated levels of IL-4, IL-5, IL-10, IL-13, GM-CSF, IFNg and TNFa, while cells obtained from whole toxin-immunized mice did not differ from baseline levels. To evaluate protective efficacy of peptides against toxin expressing strains, immunized mice were infected intravenously with MNHOCH (SEB+) or Newman (SEA+) and monitored up to 13 days. Mice that were infected with MNHOCH showed significantly extended survival compared to non-immunized mice (P=0.03). No significant difference in survival was observed when infected with strain Newman.