BioMatNet Item: FAIR-CT96-3046 - Production of recombinant immune complexes in transgenic plants for systemic and mucosal vaccines

FAIR-CT96-3046
Production of recombinant immune complexes in transgenic plants for systemic and mucosal vaccines

To find similar Items, click on a keyword below:
Biotechnology : FAIR Area 3 - Generic Science and Advanced Technologies for Nutritious Foods : Pharmaceuticals/Cosmetics : Plant Genetics

	Type of Project	Shared Cost
	Contract No	FAIR-CT96-3046
	Total Cost	750,000 ECU
	EC Contribution	750,000 ECU
	Start Date	01/10/97
	Duration	36 Months

Production of recombinant immune complexes in transgenic plants for systemic and mucosal vaccines

Objectives

Co-administration of antigen and antibody is a potent means of modulating immune reactivity, and can be used to enhance or suppress the host systemic response. Several mechanisms may be involved but complement binding and FcR binding are important, particularly as they enhance localisation and uptake by the main antigen presenting cells, macrophages, dendritic cells and B-cells. FcR binding has also been proposed as a mechanism for enhancement uptake of immune complexes through mucosal epithelium. As Fc receptors and Langerhans cells are frequently found in mucosal sites, the use of immune complexes for mucosal immunisation is a prospect for future vaccination approaches.

Technical Approach

The objectives of this proposal are:

to produce in transgenic plants, a new class of immunogenic molecule, based on antigen-antibody complexes
to perform in vitro studies of antigenicity of these molecules, by examining antigen processing and presentation to panels of specific human T-cell clones
to perform immunisation studies in mice, to examine the effects of systemic and mucosal administration, comparing the plant derived complexes with conventional antigen preparations

We propose to exploit an advantage that transgenic plants have over other simple expression systems in being able to express and assemble complex full-length antibodies in large amounts. We shall use the plant expression system to produce recombinant immune complexes and molecular derivatives, which will be characterised and then tested for antigenicity and immunogenicity in comparison with conventionally produced immune complexes and antigen preparations. We will study three different antigens, tetanus toxoid - a bacterial antigen in routine use, HIV gpl20 - a human systemic viral antigen and bovine respiratory syncytial virus F-protein - a veterinary mucosal viral antigen. In all cases, systemic models of immunisation have been established, in addition for gp120 and F-protein mucosal routes of immunisation are appropriate and may be preferred.

The antigenicity studies will examine uptake and processing by macrophages and dendritic cells, followed by presentation to specific T cell clones. The panel of human T cell clones will be derived from naive and naturally infected individuals which will help to determine the fine specificity of T-cell epitope processing following uptake of plant immune complexes. Immunisation studies will be performed in mice to establish the immunogenicity of the plant immune complexes and the efficacy of administration by both systemic and mucosal (oral, nasal and anal) routes will be studied.

New vaccines are in demand, in addition there is an important requirement for vaccines with enhanced immunogenicity as well as those that can be administrated by mucosal routes, as recognised by the FAIR programme. In this proposal, we are using plants to engineer molecules that we expect to have applications in systemic and mucosal vaccinology. This may help to establish a role for molecular farming in the production of human and veterinary vaccines.

Results to Date

Genetic constructs have been completed and the first of these have been used to transform tobacco plants. The panel of T-cell clones have been prepared.

Contacts

Coordinator

Julian MA / United Medical and Dental School Immunology Dept, Guy's Hospital / UNITED KINGDOM

Participant