Improvement of Anti-Tumor DNA Vaccination by Co-Immunization at a Distant Site with a Plasmid Encoding the Hemagglutinin-Neuraminidase Protein of Newcastle Disease Virus

Abstract

DNA vaccine encoding tumor associated antigens (TAAs) is an attractive strategy for tumor vaccine development. But its efficacy to induce efficient anti-tumor immunity needs to be improved. In this study, we combined immunization with such a plasmid at the ear pinna site (i.e.) with co-immunization with another plasmid (pHN) encoding the Hemaglutinin-Neuraminidase (HN) protein of the NDV virus at a subcutaneous site. We first tested a prophylactic immunization protocol followed by subcutaneous challenge with the ESb-lacZ lymphoma expressing the 􀀂-galactosidase protein as a surrogate tumor antigen. While i.e. vaccination with the placZ plasmid reduced tumor growth, the additional s.c. immunization with the pHN plasmid further improved this effect. We next tested a therapeutic tumor model based on the mammary carcinoma DA3-hEpCAM expressing the human EpCAM molecule. Efficient reduction of tumor growth was achieved by immunization of tumor-bearing mice with DNA plasmids encoding the human EpCAM gene only when it was combined with s.c. application of the pHN plasmid. A significantly better cross-protection against a second challenge with the parental DA3 tumor cells was only observed when mice were initially co-immunized with both plasmids. These results demonstrate that co-immunization of a plasmid encoding the HN protein of NDV and a DNA vaccine encoding a tumor antigen significantly reduced tumor growth in mouse tumor models employing both prophylactic and therapeutic vaccination strategies. These observations point towards the HN protein of NDV as a powerful molecular adjuvant for DNA vaccines.