Evaluation of mucosal vaccination with live, attenuated mutant bovine respiratory syncytial viruses

Lead Research Organisation: THE PIRBRIGHT INSTITUTE

Department Name: UNLISTED

Abstract

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Technical Summary

The principal scientific objectives are to: 1. Determine the effects of mucosal vaccination with live, attenuated mutant BRSV on the magnitude and duration of BRSV-specific CD4+ and CD8+ T-cell memory; 2 Determine the effects of mucosal vaccination with live, attenuated mutant BRSV on the magnitude and duration of BRSV-specific antibodies in serum and nasal secretions; 3. Determine the duration of protective immunity induced by mucosal vaccination with live, attenuated mutant BRSV; 4. Investigate the interaction of Mycoplasma bovis with bovine airway epithelial cells and macrophages.

Planned Impact

unavailable

Funded Value:

£84,856

Funded Period:

Mar 07 - Mar 10

Funder:

BBSRC

Project Status:

Closed

Project Category:

Institute Project

Project Reference:

BBS/E/I/00001325

Principal Investigator:

Geraldine Taylor

Research Topic:

Unclassified

Organisations

THE PIRBRIGHT INSTITUTE (Lead Research Organisation)

People	ORCID iD
Geraldine Taylor (Principal Investigator)

Publications

Author Name Title

Publication Date Published

10 25 50

Taylor G (2014) Recombinant bovine respiratory syncytial virus with deletion of the SH gene induces increased apoptosis and pro-inflammatory cytokines in vitro, and is attenuated and induces protective immunity in calves. in The Journal of general virology

Blodörn K (2014) Vaccine safety and efficacy evaluation of a recombinant bovine respiratory syncytial virus (BRSV) with deletion of the SH gene and subunit vaccines based on recombinant human RSV proteins: N-nanorings, P and M2-1, in calves with maternal antibodies. in PloS one

Key Findings
Impact Summary
Further Funding


Description	The immunogenicity and protective efficacy of mucosal vaccination of calves with six attenuated recombinant bovine respiratory syncytial virus (BRSV) against BRSV challenge were compared, 6 months after vaccination. These studies demonstrated that intranasal and intratracheal inoculation of 2 to 4 week-old, BRSV-seronegative, calves with rBRSV lacking the SH protein (rBRSV?SH) provided complete protection against subsequent challenge with virulent BRSV, whereas protection induced by the other 5 mutant rBRSV was incomplete. Furthermore, analysis of the antibody and T-cell responses induced by the various mutant BRSV suggested that BRSV-specific IgA in nasal secretions at the time of challenge correlated with protection against replication of the challenge virus in the nasopharynx. Preliminary studies analysing the interaction of the mutant rBRSV with bovine alveolar macrophages and monocytes suggested that the induction of certain pro-inflammatory cytokines by rBRSV?SH may play a role in the development of the protective adaptive immune response. However, further studies are needed to investigate this hypothesis.
Exploitation Route	Further studies are needed to determine the protective efficacy of rBRSV?SH when administered by the intranasal route alone and the effects of maternally-derived BRSV-specific antibodies on induction of protective immunity.
Sectors	Agriculture Food and Drink


Description	A mutant bovine respiratory syncytial virus lacking the SH gene, which was shown to be attenuated in calves and induce protection against challenge with virulent virus has been licensed to a Veterinary Pharmaceutical company with a view to further evaluation as a commercial vaccine.
First Year Of Impact	2010
Sector	Agriculture, Food and Drink


Description	Horizon 2020
Amount	€ 239,067 (EUR)
Funding ID	633184
Organisation	European Commission
Sector	Public
Country	Belgium
Start	03/2015
End	02/2019