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Development of Delivery by Schistosomes of Broadly Neutralizing Anti-HIV-1 Antibody

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Introduction. The overarching goal of this study is to determine whether a long-lived, transgenic helminth parasite might express a potentially therapeutic antibody, using HIV-1 as the model target of a broadly neutralizing antibody expressed and secreted by schistosomes.Methods. Cultured schistosomes were transfected by square wave electroporation with a plasmid encoding a human immunoglobulin G1 that is broadly neutralizing for HIV-1. Results. Following introduction of an expression plasmid into cultured schistosomes by square wave electroporation, and extraction of total RNA and soluble lysates of the parasites, transcripts encoding both the light and heavy chains of the anti-HIV-1 broadly neutralizing antibody b12 and fragments of the human IgG1 antibody b12 were detected by reverse transcription PCR and western blot analysis, respectively.Conclusions. These findings revealed that a human antibody, which is known to be broadly neutralizing for HIV-1, was expressed in schistosomes. Whereas this investigation is a work in progress, the findings thus far provide impetus to explore whether schistosomes transgenic with the gene encoding b12 might be harnessed to inhibit HIV-1 infection in vivo.

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