Plant-derived chimeric antibodies inhibit the invasion of human fibroblasts by Toxoplasma gondii

Sherene Swee Yin Lim, Kek Heng Chua, Greta Nölke, Holger Spiegel, Wai Leong Goh, Sek Chuen Chow, Boon Pin Kee, Rainer Fischer, Stefan Schillberg, Rofina Yasmin Othman

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    3 Citations (Scopus)

    Abstract

    The parasite Toxoplasma gondii causes an opportunistic infection, that is, particularly severe in immunocompromised patients, infants, and neonates. Current antiparasitic drugs are teratogenic and cause hypersensitivity-based toxic side effects especially during prolonged treatment. Furthermore, the recent emergence of drug-resistant toxoplasmosis has reduced the therapeutic impact of such drugs. In an effort to develop recombinant antibodies as a therapeutic alternative, a panel of affinity-matured, T. gondii tachyzoite-specific single-chain variable fragment (scFv) antibodies was selected by phage display and bioinformatic analysis. Further affinity optimization was attempted by introducing point mutations at hotspots within light chain complementarity-determining region 2. This strategy yielded four mutated scFv sequences and a parental scFv that were used to produce five mouse–human chimeric IgGs in Nicotiana benthamiana plants, with yields of 33–72 mg/kg of plant tissue. Immunological analysis confirmed the specific binding of these plant-derived antibodies to T. gondii tachyzoites, and in vitro efficacy was demonstrated by their ability to inhibit the invasion of human fibroblasts and impair parasite infectivity. These novel recombinant antibodies could therefore be suitable for the development of plant-derived immunotherapeutic interventions against toxoplasmosis.

    Original languageEnglish
    Article numbere5780
    Number of pages31
    JournalPeerJ
    Volume6
    DOIs
    Publication statusPublished - 11 Dec 2018

    Keywords

    • IgG
    • Parasite
    • Phage display
    • Plantibodies
    • ScFv
    • Tachyzoites

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