The University of Southampton
University of Southampton Institutional Repository

Amplification of immune responses against a DNA-delivered idiotypic lymphoma antigen by fusion to the B subunit of E.coli heat labile toxin

Amplification of immune responses against a DNA-delivered idiotypic lymphoma antigen by fusion to the B subunit of E.coli heat labile toxin
Amplification of immune responses against a DNA-delivered idiotypic lymphoma antigen by fusion to the B subunit of E.coli heat labile toxin
The pentameric B-subunit of Escherichia coli heat-labile enterotoxin (EtxB) is not only highly immunogenic itself, but can also act as a potent adjuvant or carrier to increase immune responses to other antigens. In this study, we investigated the ability of EtxB to promote anti-tumor immune responses using a fusion DNA vaccine design. EtxB was genetically linked to a single chain Fv sequence derived from the idiotypic immunoglobulin antigen (Id) of the mouse BCL1 B-cell lymphoma. We found that the EtxB–BCL1scFv fusion protein with a specifically selected linker retained the ability to pentamerize and to bind the GM1 ganglioside. Immunization of mice with the pEtxB–BCL1scFv DNA construct generated high levels of Id-specific antibody and protected against lethal tumor challenge. The immuno-enhancing activities of EtxB were highly dependent on GM1 binding, since fusion constructs unable to pentamerize or to bind to GM1 were less effective. Thus, the EtxB fusion vaccine approach may be an attractive strategy to increase the potency of tumor vaccines.
DNA vaccine, B-cell lymphoma, idiotype, E. coli heat-labile enterotoxin, GM1 receptor
4289-4296
Chen, Caleb G
043c7202-af25-40c6-af36-f005fadb5e01
Lu, Yen-Ta
4e1e1afd-1890-4b8c-9b89-0b76e2438fc5
Lin, Marie
82e73eaa-bafc-4d71-bf4c-f66bed0f3cf8
Savelyeva, Natalia
804c3e15-d260-4717-9b7c-15c16ba87fc7
Stevenson, Freda
ba803747-c0ac-409f-a9c2-b61fde009f8c
Zhu, Delin
49eeb78f-f607-4079-80b3-45574dc41fa5
Chen, Caleb G
043c7202-af25-40c6-af36-f005fadb5e01
Lu, Yen-Ta
4e1e1afd-1890-4b8c-9b89-0b76e2438fc5
Lin, Marie
82e73eaa-bafc-4d71-bf4c-f66bed0f3cf8
Savelyeva, Natalia
804c3e15-d260-4717-9b7c-15c16ba87fc7
Stevenson, Freda
ba803747-c0ac-409f-a9c2-b61fde009f8c
Zhu, Delin
49eeb78f-f607-4079-80b3-45574dc41fa5

Chen, Caleb G, Lu, Yen-Ta, Lin, Marie, Savelyeva, Natalia, Stevenson, Freda and Zhu, Delin (2009) Amplification of immune responses against a DNA-delivered idiotypic lymphoma antigen by fusion to the B subunit of E.coli heat labile toxin. Vaccine, 27 (32), 4289-4296. (doi:10.1016/j.vaccine.2009.05.025).

Record type: Article

Abstract

The pentameric B-subunit of Escherichia coli heat-labile enterotoxin (EtxB) is not only highly immunogenic itself, but can also act as a potent adjuvant or carrier to increase immune responses to other antigens. In this study, we investigated the ability of EtxB to promote anti-tumor immune responses using a fusion DNA vaccine design. EtxB was genetically linked to a single chain Fv sequence derived from the idiotypic immunoglobulin antigen (Id) of the mouse BCL1 B-cell lymphoma. We found that the EtxB–BCL1scFv fusion protein with a specifically selected linker retained the ability to pentamerize and to bind the GM1 ganglioside. Immunization of mice with the pEtxB–BCL1scFv DNA construct generated high levels of Id-specific antibody and protected against lethal tumor challenge. The immuno-enhancing activities of EtxB were highly dependent on GM1 binding, since fusion constructs unable to pentamerize or to bind to GM1 were less effective. Thus, the EtxB fusion vaccine approach may be an attractive strategy to increase the potency of tumor vaccines.

Full text not available from this repository.

More information

Published date: 9 July 2009
Keywords: DNA vaccine, B-cell lymphoma, idiotype, E. coli heat-labile enterotoxin, GM1 receptor

Identifiers

Local EPrints ID: 79343
URI: https://eprints.soton.ac.uk/id/eprint/79343
PURE UUID: 63f9ce70-81e2-4876-83af-6ae3efd68944
ORCID for Freda Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

Catalogue record

Date deposited: 15 Mar 2010
Last modified: 20 Jul 2019 01:16

Export record

Altmetrics

Contributors

Author: Caleb G Chen
Author: Yen-Ta Lu
Author: Marie Lin
Author: Freda Stevenson ORCID iD
Author: Delin Zhu

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×