NEUTRALIZING ACTIVITY OF HUMAN POLYCLONAL ANTIBODIES TOWARDS STAPHYLOCOCCAL AND STREPTOCOCCAL SUPERANTIGENS IN VITRO, AND IN VIVO USING A MURINE MODEL OF TOXIC SHOCK

Abstract

Staphylococcal and streptococcal superantigens (SAgs) are the causes of toxic shock syndrome (TSS), a serious life threatening condition often resulting from staphylococcal and streptococcal infections. Intravenous Immunoglobulin (IVIG) preparations, containing antibodies against SAgs, have been used as adjunctive therapy to antibiotics in TSS cases, however with limited success.

To exhaust the potential of SAg-specific polyclonal antibodies (pAbs) in treatment of TSS, pAbs towards the staphylococcal SAgs SEA, SEB, SED, TSST-1, and streptococcal SpeA and SpeC were affinity-purified from IVIG and their SAg-neutralizing and cross-neutralizing potential, alongside that of IVIG, were tested in vitro using human peripheral blood mononuclear cells (PBMCs) and in vivo in a murine model of toxic shock. Our results showed that these purified pAbs had on average a 100-fold better toxin neutralizing activity than IVIG in vitro. Purified pAbs also provided better protection to toxin-challenged mice than IVIG. The degree of cross-neutralization towards toxins with similar primary structure was shown to be high.