Depletion of T cell epitopes in lysostaphin mitigates anti-drug antibody response and enhances antibacterial efficacy in vivo.

ABSTRACT: The enzyme lysostaphin possesses potent anti-staphylococcal activity and represents a promising antibacterial drug candidate; however, its immunogenicity poses a barrier to clinical translation. Here, structure-based biomolecular design enabled widespread depletion of lysostaphin DRB1(∗)0401 restricted T cell epitopes, and resulting deimmunized variants exhibited striking reductions in anti-drug antibody responses upon administration to humanized HLA-transgenic mice. This reduced immunogenicity translated into improved efficacy in the form of protection against repeated challenges with methicillin-resistant Staphylococcus aureus (MRSA). In contrast, while wild-type lysostaphin was efficacious against the initial MRSA infection, it failed to clear subsequent bacterial challenges that were c

SUBMITTER: Zhao H 

PROVIDER: S-EPMC4441767 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature