Pre-existing antibody-mediated adverse effects prevent the clinical development of a bacterial anti-inflammatory protein.

ABSTRACT: Bacterial pathogens have evolved to secrete strong anti-inflammatory proteins that target the immune system. It was long speculated whether these virulence factors could serve as therapeutics in diseases in which abnormal immune activation plays a role. We adopted the secreted chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) as a model virulence factor-based therapeutic agent for diseases in which C5AR1 stimulation plays an important role. We show that the administration of CHIPS in human C5AR1 knock-in mice successfully dampens C5a-mediated neutrophil migration during immune complex-initiated inflammation. Subsequent CHIPS toxicology studies in animal models were promising. However, during a small phase I trial, healthy human volunteers showed adverse effects directly

SUBMITTER: Tromp AT 

PROVIDER: S-EPMC7541340 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature