Award details

Genetic and immunological safety of DNA vaccines

Reference	BBS/E/I/00000386
Principal Investigator / Supervisor	Dr Geraldine Taylor
Co-Investigators / Co-Supervisors
Institution	The Pirbright Institute
Department	The Pirbright Institute Department
Funding type	Research
Value (£)	90,053
Status	Completed
Type	Institute Project
Start date	01/04/1997
End date	30/09/1999
Duration	30 months

Abstract

RSV is the single most common cause of viral bronchiolitis in young children. Although the development of a vaccine against RSV is a high priority, no effective vaccine against human RSV is available. Indeed, vaccine development has proceeded with caution following the spectre of vaccine- augmented disease. In a murine model of RSV infection, prior sensitisation with the G protein leads to a Th2 response that is associated with pulmonary eosinophilia, a predominant CD4+ T cell recruitment in broncho-alveolar lavage (BAL) and enhanced illness following RSV challenge. In order to determine if DNA that encodes the G protein (G- DNA) could protect mice from RSV challenge and avoid the Th2-associated pathology, mice were given 3 intramuscular injections of plasmid DNA at weekly intervals. Mice vaccinated with G-DNA had a significantly reduced virus load in their lungs 5 days after RSV challenge compared with control mice. The effect of co-immunisation with DNA encoding the cytokines IL-2 and IL-4 on the immune responses to G-DNA was assessed by comparing RSV-specific antibody isotypes. Mice immunised with GDNA alone had a trend towards IgG1 > IgG2a. This was more pronounced in mice co-immunised with DNA encoding IL-4. In contrast, mice co-immunised with DNA encoding IL-2 had a predominant IgG2a antibody isotype. These data suggest that vaccine-enhanced illness observed following sensitisation with the G protein can be avoided by the use of plasmid DNA that encodes the full-length wild- type protein. Furthermore, DNA encoding plasmids have the ability to modulate the types of immune response induced by proteins encoded on separate plasmid vectors.

Summary

unavailable

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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