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

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. ¹⁷⁶ EFNN ¹⁷⁹ ) of SEB recognized by LXY8. The research revealed that the ¹⁷⁶ EFNN ¹⁷⁹ 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.
Competing Interests: Declaration of competing interest Long L. Luo, Nai J. Hu, Chun X. Qiao, Jing Wang, Xin Y. Li, Jan N. Feng and Bei F. Shen have submitted patent applications pertaining to anti-SEB antibodies. The other authors declare no conflict of interest.
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