title: Phage and Yeast Display.
abstract: Despite the availability of antimicrobial drugs, the continued development of microbial resistance--established through escape mutations and the emergence of resistant strains--limits their clinical utility. The discovery of novel, therapeutic, monoclonal antibodies (mAbs) offers viable clinical alternatives in the treatment and prophylaxis of infectious diseases. Human mAb-based therapies are typically nontoxic in patients and demonstrate high specificity for the intended microbial target. This specificity prevents negative impacts on the patient microbiome and avoids driving the resistance of nontarget species. The in vitro selection of human antibody fragment libraries displayed on phage or yeast surfaces represents a group of well-established technologies capable of generating human mAbs. The advantage of these forms of microbial display is the large repertoire of human antibody fragments present during a single selection campaign. Furthermore, the in vitro selection environments of microbial surface display allow for the rapid isolation of antibodies--and their encoding genes--against infectious pathogens and their toxins that are impractical within in vivo systems, such as murine hybridomas. This article focuses on the technologies of phage display and yeast display, as these strategies relate to the discovery of human mAbs for the treatment and vaccine development of infectious diseases.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215.
authors.forename: Jared
authors.initials: J
authors.lastname: Sheehan
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215.
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Marasco
mesh_terms: D000911:Antibodies, Monoclonal / Q000235:genetics / Q000302:isolation & purification / Q000627:therapeutic use; D001435:Bacteriophages / Q000235:genetics* / Q000378:metabolism*; D061505:Cell Surface Display Techniques / Q000379:methods*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D015003:Yeasts / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D008565:Membrane Proteins; D011994:Recombinant Proteins