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Fool me twice... A novel 'Trojan horse' antibody circumvents ebolavirus infections

September 08, 2016

Scientists have shown that a two-pronged antibody can counteract the unique immune-evasion mechanism that filoviruses like Ebola have evolved. This is a critical step on the road to developing treatments that protect broadly against ebolaviruses, for which there remains an urgent need. Filoviruses including Ebola have an unusual route into the host cell; they access the inside of cells through tiny transport vesicles, or endosomes, where they interact with a specific host-cell receptor called NPC1, and then become unmasked. In effect, this two-step pathway acts as a shield -- hiding the virus from the immune system and hindering the potency of anti-viral therapies. In search of a way to counter this evolved immune evasion mechanism, Anna Wec and colleagues engineered a bispecific antibody to first bind a specific glycoprotein (GP) on the outside of the virus, and ride along with it, much like a Trojan horse. It could then attach to NPC1 in the endosome, preventing GP from associating with NPC1 and releasing Ebola into host cells. In human cell lines, Wec et al. confirmed the neutralizing activity of the antibodies across all known ebolaviruses, demonstrating their potential as a solution to treating Ebola broadly. They also evaluated the efficacy of the antibodies in mouse models, finding that 70% of mice were able to survive multiple types of Ebola infection two days after a lethal challenge, compared to the untreated control group. Bispecific antibody systems could also prove useful against other viral pathogens known to hijack intracellular receptors, such as Lassa virus, the authors say.
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American Association for the Advancement of Science

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