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
Jing Ni1, Volker Schirrmacher1, 2, *, Philippe Fournier1, *
Identifiers and Pagination:Year: 2010
First Page: 15
Last Page: 21
Publisher Id: TOCIJ-3-15
Article History:Received Date: 21/04/2010
Revision Received Date: 24/06/2010
Acceptance Date: 09/07/2010
Electronic publication date: 11/11/2010
Collection year: 2010
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.