title: Genetic fusions with viral chemokines target delivery of nonimmunogenic antigen to trigger antitumor immunity independent of chemotaxis.
abstract: The ideal vaccine carrier should be able to target antigen delivery and possibly recruit antigen-presenting cells (APC) and deliver an activation signal to promote adaptive immune responses. Ligands for chemokine receptors expressed on APC may be attractive candidates, as they can both target and attract APC. To investigate the requirement for APC recruitment, we used a pair of viral chemokines, agonist herpes simplex virus 8-derived macrophage inflammatory protein-I (vMIP-I) and antagonist MC148, which induce and suppress chemotaxis, respectively. Chemokine-antigen fusions efficiently delivered a model nonimmunogenic tumor antigen to APC for processing and presentation to antigen-specific T cells in vitro. Physical linkage of chemokine and antigen and specific binding of chemokine receptor by the fusion protein were required. Mice immunized with vMIP-I or MC148 fusion DNA vaccines elicited protection against tumor challenge. Therefore, vaccine efficacy depends primarily on the ability of the carrier to target antigen delivery to APC for subsequent processing and presentation, and chemotaxis directly induced by the chemokine moiety in the fusion may not be necessary.
authors.affiliation: Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Pier Adelchi
authors.initials: PA
authors.lastname: Ruffini
authors.forename: Arya
authors.initials: A
authors.lastname: Biragyn
authors.forename: Marta
authors.initials: M
authors.lastname: Coscia
authors.forename: Linda K
authors.initials: LK
authors.lastname: Harvey
authors.forename: Soung-Chul
authors.initials: SC
authors.lastname: Cha
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
authors.forename: Larry W
authors.initials: LW
authors.lastname: Kwak
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D018925:Chemokines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D019742:Chemokines, CC / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D003001:Cloning, Molecular; D016503:Drug Delivery Systems / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D008223:Lymphoma / Q000276:immunology / Q000517:prevention & control*; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D019444:Vaccines, DNA / Q000008:administration & dosage; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018925:Chemokines; D019742:Chemokines, CC; C435144:MC148 protein, poxvirus molluscum contagiosum; D019402:Macrophage Inflammatory Proteins; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D014764:Viral Proteins; C108459:vMIP-1 protein, Human herpesvirus 8