title: Instant immunity through chemically programmable vaccination and covalent self-assembly.
abstract: The ability to instantly create a state of immunity as achieved in the passive transfer of hyperimmune globulin has had a tremendous impact on public health. Unlike passive immunization, active immunization, which is the foundation of vaccinology, is an anticipatory strategy with inherent limitations. Here we show that elements of active and passive immunization can be combined to create an effective chemistry-driven approach to vaccinology. Reactive immunization was used to create a reservoir of covalent polyclonal antibodies in 3 mouse strains that were subsequently engrafted with syngeneic CT26 colon or B16F10 melanoma tumors. Upon administration of designed integrin alpha(v)beta(3) and alpha(v)beta(5) adapter ligands, the induced covalent polyclonal antibodies self-assembled with the adapter ligands and the animals mounted an instant, chemically programmed, polyclonal response against the implanted tumors. Significant therapeutic responses were observed without recourse to adjuvant therapy. The chemically programmed immune responses were driven by antibody-dependent cellular cytotoxicity and complement-directed cytotoxicity. We suggest that this type of chemistry-driven approach to vaccinology is underexplored and may provide routes to vaccines to protect against diseases that have proven intractable to biology-driven vaccine approaches.
authors.affiliation: The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Popkov
authors.forename: Beatriz
authors.initials: B
authors.lastname: Gonzalez
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Sinha
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Barbas
mesh_terms: D000818:Animals; D000917:Antibody Formation; D000920:Antibody-Dependent Cell Cytotoxicity; D019496:Cancer Vaccines; D003110:Colonic Neoplasms / Q000517:prevention & control / Q000628:therapy; D003167:Complement Activation; D007109:Immunity / Q000187:drug effects*; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors; D008024:Ligands; D008546:Melanoma, Experimental / Q000517:prevention & control / Q000628:therapy; D051379:Mice; D009374:Neoplasms, Experimental; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors; D014612:Vaccines / Q000737:chemistry*
chemical_list: D019496:Cancer Vaccines; D039302:Integrin alphaVbeta3; D008024:Ligands; D019030:Receptors, Vitronectin; D014612:Vaccines; C064660:integrin alphaVbeta5