Abstract: PB10 IgG1, a monoclonal antibody (MAb) directed against an immunodominant epitope\non the enzymatic subunit (RTA) of ricin toxin (RT), has been shown to passively protect mice\nand non-human primates from an aerosolized lethal-dose RT challenge. However, it was\nrecently demonstrated that the therapeutic efficacy of PB10 IgG1 is significantly improved when\nco-administered with a second MAb, SylH3, targeting RTâ??s binding subunit (RTB). Here we report that\nthe PB10/SylH3 cocktail is also superior to PB10 alone when used as a pre-exposure prophylactic (PrEP)\nin a mouse model of intranasal RT challenge. The benefit of the PB10/SylH3 cocktail prompted us to\nengineer a humanized IgG1 version of SylH3 (huSylH3). The huPB10/huSylH3 cocktail proved highly\nefficacious in the mouse model, thereby opening the door to future testing in non-human primates.
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