CpG ODN 1826 Enhances the Efficacy of Idiotype DNA Vaccine Administered Intrasplenically

ABSTRACT

Effectiveness of intrasplenic administration of plasmid vaccines has been of interest in vaccine research, because the spleen is strategically located to filter antigens in circulation and provides the milieu to mount vigorous immune responses against trapped antigens. Intrasplenic vaccination with the naked plasmid DNA and a Cytosine Phosphorothiolated Guanine (CpG) adjuvant is expected to engender lasting effects. Specific unmethylated CpGcontaining Oligodeoxynucleotides (CpG ODN) can serve as a danger signal to the vertebrate immune system. This study was initiated to evaluate a single chain variable fragment (scFv) construct (Id-Th) which encodes the Id of a murine lymphoma 2C3-associated immunoglobulin (Ig) and a T helper epitope. Our previous studies show that scFv plasmid expressing 2C3 idiotype are processed and recognized by Id-specific cytotoxic T-lymphocytes in vitro, but in vivo they evoke only moderate responses when administered by intramuscular or intradermal routes. In this report, we addressed the effectiveness of Id-Th, a new 2C3 Id DNA vaccine, delivered intrasplenically. We show here that, after intra-splenic immunization of Id-Th, the appearance of Id-antigen in sera of tumor-challenged mice is significantly delayed (52.4% decrease), 36.8% of mice survive a challenge of 1x10³ live 2C3 tumor cells. Furthermore, inclusion of CpG ODN 1826 as adjuvant further improves vaccine efficiency and delays the appearance of Id-antigen (64.9% decrease), and enhances the survival rate by 53.8%. In summary, intrasplenic delivery of DNA vaccines with CpG adjuvant is a potentially useful immunotherapeutic modality and the mechanism remains to be investigated.

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