Genetically engineered two-warhead evasins provide a method to achieve precision targeting of disease-relevant chemokine subsets

Sci Rep. 2018 Apr 20;8(1):6333. doi: 10.1038/s41598-018-24568-9.


Both CC and CXC-class chemokines drive inflammatory disease. Tick salivary chemokine-binding proteins (CKBPs), or evasins, specifically bind subsets of CC- or CXC-chemokines, and could precisely target disease-relevant chemokines. Here we have used yeast surface display to identify two tick evasins: a CC-CKBP, P1243 from Amblyomma americanum and a CXC-CKBP, P1156 from Ixodes ricinus. P1243 binds 11 CC-chemokines with Kd < 10 nM, and 10 CC-chemokines with Kd between 10 and 100 nM. P1156 binds two ELR + CXC-chemokines with Kd < 10 nM, and four ELR + CXC-chemokines with Kd between 10 and 100 nM. Both CKBPs neutralize chemokine activity with IC50 < 10 nM in cell migration assays. As both CC- and CXC-CKBP activities are desirable in a single agent, we have engineered "two-warhead" CKBPs to create single agents that bind and neutralize subsets of CC and CXC chemokines. These results show that tick evasins can be linked to create non-natural proteins that target subsets of CC and CXC chemokines. We suggest that "two-warhead" evasins, designed by matching the activities of parental evasins to CC and CXC chemokines expressed in disease, would achieve precision targeting of inflammatory disease-relevant chemokines by a single agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Arachnida / metabolism
  • Chemokines / metabolism
  • Chemokines, CC / metabolism
  • Chemokines, CXC / metabolism
  • Genetic Engineering
  • HEK293 Cells
  • Humans
  • Protein Binding
  • Receptors, CXCR / genetics
  • Receptors, CXCR / metabolism*
  • Receptors, Chemokine / metabolism*
  • Saccharomyces cerevisiae / metabolism
  • THP-1 Cells
  • Ticks / metabolism*


  • Chemokines
  • Chemokines, CC
  • Chemokines, CXC
  • Receptors, CXCR
  • Receptors, Chemokine