Biomedicine

Mounting a Counterattack

Science  21 Apr 2006:
Vol. 312, Issue 5772, pp. 338
DOI: 10.1126/science.312.5772.338a

Although pathogens display a remarkable ability to out-maneuver host defenses, this struggle has been described as a never-ending arms race. Through antigenic variation of their variant surface glycoproteins (VSGs), trypanosomes successfully evade host immune responses, rendering prevention via vaccination difficult at best. Baral et al. have engineered the latest attempt to combat Trypanosoma brucei, the causative agent of sleeping sickness, which is transmitted via the tsetse fly. One component of human serum, apoL-I, has been identified as being able to punch holes in most trypanosomes but is stymied by the serum resistance-associated (SRA) protein produced by the resistant strain T. b. rhodesiense. The authors chopped off the portion of apoL-I to which SRA binds and attached the rest to an antibody that recognizes VSGs. This conjugate proved efficacious in lysing trypanosomes in vitro and in curing mice suffering from an acute infection by T. b. rhodesiense, and it also completely cleared parasites from the bloodstream in chronically infected mice. — GJC

Nat. Med. 12, 10.1038/nm1395 (2006).

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