Identification of a novel protective human monoclonal antibody, LXY8, that targets the key neutralizing epitopes of staphylococcal enterotoxin B

Abstract

Staphylococcal enterotoxin B (SEB), one of the exotoxins produced by Staphylococcus aureus, is the key toxin that causes poisoning reactions and toxic shock syndrome. In the current research work, a novel human antibody named LXY8 was screened from a human phage display antibody library, and LXY8 blocked the interaction between SEB and the T cell receptor (TCR). The binding activity between LXY8 and SEB was 0.525 nM. Furthermore, LXY8 could effectively inhibit the SEB-induced activation of peripheral blood mononuclear cells and release of cytokines. In the BALB/c mouse model, LXY8 effectively neutralized SEB toxicity in vivo. Finally, based on computer-guided molecular modeling, we designed a series of SEB mutation sites; these sites facilitated the determination of the key residues (i.e.¹⁷⁶EFNN¹⁷⁹) of SEB recognized by LXY8. The research revealed that the ¹⁷⁶EFNN¹⁷⁹ residues of SEB are important for specific antibody-antigen recognition. The results may be helpful for the development of antibody-based therapy for SEB-induced toxic shock syndrome.

Keywords: Neutralizing antibody; Staphylococcal enterotoxin B; Treatment.