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Recombinant bacillovirus expressed particulate vehicles as multiple epitopes presentation systems

Objective

The project concerns development of safe and non-replicating effective multivalent vaccines for animal and human pathogens. These are to be realised by utilizing genetically engineered non-infectious empty protein capsids based (recombinant baculovirus synthesised) on bluetongue virus (BTV) articles (CLPs, VLPs) and porcine parvovirus capsids. These capsid structures have high immunogenic and protective activities. The objective is twofold: (1) to identify the regions on the capsid proteins that would allow the insertion of short immunogenic (B and T cell) epitopes of infectious agents, (2) to determine the capacities and efficacies of the chimeric capsid structure for protection against infectious agents.
The core-like (CLPs) are assembled by two proteins, VP3 and VP7, with VP7 being the surface layer of the capsid. On the basis of recent three dimensional X-ray crystallographic structures of VP7 forming two sites within this molecule have been identified for extra sequence insertion. Both B and T cell epitopes from several viruses (Bovine leukemia virus, BLV, Polio, Lymphocytic choriomeningitis virus, LCMV, Influenza, etc.) have been inserted and assembly of the chimeric CLPs, their biochemical and immunological properties were investigated. The data suggested that CLPs have the capacity to elicit both B and T cell immune responses and thus can be used as vaccine delivery systems. The VLPs structure has another capsid of two proteins (VP2 and VP5) of BTV surrounding the CLPs. The outermost protein VP2, which is has been analysed by computer modelling and subsequently, by mutagenesis analysis for localising the dispensable sequences. The results indicated at least four regions within VP2 molecules are available to localise, which can be substituted by immunogenic epitopes. Currently, these regions are being exploited for carrying protective immunogens of various infectious agents.
Several antigenic sites have been identified in the N-terminus of the PPV protein VP2, which assemble into a capsid structure when expressed by baculovirus vector system. Some of these regions have been manipulated to carry foreign sequences such as B and T cell epitope of Polio and LCMV. The chimeric particles were tested for their immunogeneity and the results obtained indicated that while significant T cell responses were achieved by these chimeras, the particles failed to elicit B cell responses. Further studies for identifying the suitable regions for B cell epitope insertion are now under investigation.

SCIENTIFIC BREAKTHROUGHS:
It has been demonstrated that both chimeric CLPs and PPV capsids have the ability to elicit cellular and humoral immunity against a number of infectious agents and thus can be developed as efficacious vaccine delivery systems.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

The Chancellor, Masters and Scholars of the University of Oxford
Address
South Parks Road
OX1 3QU Oxford
United Kingdom

Participants (5)

Faculté Universitaire des Sciences Agronomiques de Gembloux
Belgium
Address
13,Avenue Maréchal Juin 13
5030 Gembloux
INMUNOLOGIA Y GENETICA APLICADA SA
Spain
Address
Hermanos Garcia Noblejas 41
Madrid
Institut Pasteur
France
Address
25 Rue Du Docteur Roux
75015 Paris
PHILIPPS UNIVERSITY MARBURG
Germany
Address
Robert Kochstrasse 17
35037 Marburg
Université de Paris VI (Université Pierre et Marie Curie)
France
Address
4 Place Jussieu
75252 Paris