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

Lead Research Organisation: The Pirbright Institute
Department Name: UNLISTED

Abstract

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.
 
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 European Union (EU)
Start 03/2015 
End 02/2019