Engineered
anthrax proteins for targeted vaccine delivery into
cross-presenting dendritic cells. (A) Designs of the engineered components:
triple mutant protective antigen (mPAC), which enables side-chain
bioconjugation and ablates binding to native anthrax receptors; single-chain
variable fragment (scFv), which recognizes the XCR1 receptor; and
a linker peptide (dotted line), which connects the scFv and mPAC.
(B) Envisioned mechanism of translocation for scFv-mPAC (scFv-mPAC83), which exhibits recognition of the XCR1 receptor, proteolytic
cleavage (scFv-mPAC63), oligomerization (scFv-mPAC)7, and cytosolic delivery of the N-terminus of lethal factor
(LFN) with an appended antigen peptide (red).