Giuseppe
Emeritus
Abstract. Instant immunity through chemically programmable vaccination and covalent self-assembly.
Instant immunity through chemically programmable vaccination and covalent self-assembly
[Free Full PDF Document at LINK. EDITED.]
Mikhail Popkov, Beatriz Gonzalez, Subhash C. Sinha, and Carlos F. Barbas, III1
The Skaggs Institute for Chemical Biology and the Departments of Molecular Biology and Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037
Communicated by Richard A. Lerner, The Scripps Research Institute, La Jolla, CA, January 7, 2009 (received for review December 12, 2008)
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.
aldolase - angiogenesis - colon cancer - melanoma - tolerance
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Instant immunity through chemically programmable vaccination and covalent self-assembly
[Free Full PDF Document at LINK. EDITED.]
Mikhail Popkov, Beatriz Gonzalez, Subhash C. Sinha, and Carlos F. Barbas, III1
The Skaggs Institute for Chemical Biology and the Departments of Molecular Biology and Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037
Communicated by Richard A. Lerner, The Scripps Research Institute, La Jolla, CA, January 7, 2009 (received for review December 12, 2008)
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.
aldolase - angiogenesis - colon cancer - melanoma - tolerance
-
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