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Content archived on 2024-04-30

Self limiting vectors, based on defective corona viruses, as generic vaccines against mucosal infections

Objective



The objective is: to develop safe, replicating but self-limiting viral vector vaccines (virus vectors with mini-genomes) against a wide range of porcine and avian pathogens.
based on porcine and avian corona virus defective RNAs .
assembled into virus particles using packaging cell lines.
Coronaviruses are enveloped, positive-sense (approx. 30kb) RNA viruses. We shall use avian infectious bronchitis virus (IBV) and porcine transmissible gastroenteritis virus (TGEV) of which we (partners 1 and 2) have isolated, cloned and rescued defective RNAs (approx. 10 kb). These "mini-genomes" possess 5' and 3' genomic sequences, part of the polymerase gene, including packaging signal, but lack structural protein genes. Heterologous genes properly inserted into such mini- genomes have been shown for murine corona viruses to be expressed. Assembly of virus-like particles from co-expressed structural proteins of murine and feline corona viruses has been demonstrated by partner 3. We propose to prepare IBV and TGEV mini-genomes with complete polymerase genes, to insert into these replicating RNAs genes from corona viruses AND other pathogens, to package these genomes in cells expressing the structural proteins, and to immunise chickens and pigs oronasally with these defective viruses in order to induce a protective mucosal immune response. These vectors essentially meet all the present-day requirements: They acquire their targeting to mucosal surfaces from their envelope proteins being derived from a "mucosal" virus; They acquire their replicating ability from the encapsidated coronaviral polymerase gene contained in the mini genome; They acquire their vaccine specificity from the gene(s) contained in and expressed by the mini genome; They acquire their safety from their inability to produce new virus or spread, being limited to one round of replication; They acquire their potency by their ability to induce both humoral and cellular immune responses; They acquire their versatility by their ability to express any "immunogene", singly or in combination, including cytokine genes. This work will also extend our understanding of basic aspects of corona virus biology, and the immunogenicity of proteins of MANY pathogens following expression at mucosal surfaces.

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Coordinator

INSTITUTE FOR ANIMAL HEALTH
EU contribution
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High street,Compton
RG20 7NN NEWBURY
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Participants (3)

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