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Published online before print April 9, 2004
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,1
,
Laboratory of Immunology, National Institute on Aging, Baltimore, Maryland;
|| Experimental Transplantation and Immunology Branch, National Cancer Institute, Frederick, Maryland;
Intramural Research Support Program, Science Applications International Corporation-Frederick, Maryland;
¶ Institute of Immunology, University of Oslo, National Hospital, Norway;
* Divisione di Oncologia Medica Falck, Ospedale Niguarda Ca’ Granda, Milan, Italy (on leave of absence); and
Divisione di Ematologia dell’Universita’ di Torino, Laboratorio di Ematologia Oncologica, CeRMS, Azienda Ospedaliera San Giovanni Battista, Torino, Italy (on leave of absence)
1Correspondence: Laboratory of Immunology, National Institute on Aging, Baltimore, MD 21224. E-mail: biragyna{at}grc.nia.nih.gov
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.
Key Words: MC148 • vMIP-I • viral chemokine antagonist • APC targeting • vaccine carrier • lymphoma
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