Submitted June 30, 2006
Accepted May 29, 2007
Chemokine-idiotype fusion DNA vaccines are potentiated by bivalency and xenogeneic sequences
Agnete Brunsvik Fredriksen* and Bjarne Bogen
Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway
* Corresponding author; email: a.b.fredriksen{at}medisin.uio.no.
V regions of monoclonal Ig express an exquisite B cell tumor-specific antigen called idiotype (Id). Id is a weak antigen and it is important to improve immunogenicity of Id vaccines. Chemokine receptors are expressed on APC and are promising targets for Id vaccines. Here we compare monomeric and dimeric forms of MIP-1
and RANTES that target Id to APC in a mouse B lymphoma (A20) and a multiple myeloma model (MOPC315). MIP-1 was more potent than RANTES. The dimeric proteins were more potent than monomeric equivalents in short-term assays. When delivered in vivo by i.m. injection of plasmids followed by electroporation, dimeric proteins efficiently primed APC in draining lymph nodes for activation and proliferation of Id-specific CD4+ T cells. Good anti-Id antibody responses were obtained, and mice immunized only once were 60-80% protected in both tumor models. CD8+ T cells contributed to the protection. Antibody responses and tumor protection were reduced when the human Ig hinge+CH3 dimerization motif was replaced with syngeneic mouse counterparts, indicating that tumor protective responses were dependent on xenogeneic sequences. The results suggest that bivalency and foreign sequences combine to increase the efficiency of chemokine-Id DNA vaccines.
