Premium
Genetic fusions with viral chemokines target delivery of nonimmunogenic antigen to trigger antitumor immunity independent of chemotaxis
Author(s) -
Ruffini Pier Adelchi,
Biragyn Arya,
Coscia Marta,
Harvey Linda K.,
Cha SoungChul,
Bogen Bjarne,
Kwak Larry W.
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1003481
Subject(s) - biology , chemokine , antigen presentation , chemotaxis , antigen , antigen processing , chemokine receptor , immunology , cross presentation , immune system , t cell , receptor , biochemistry
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.