Project: Development and comparative evaluation of three new generation BRSV DIVA vaccines and a corresponding DIVA test
"Bovine Respiratory Syncytial Virus (BRSV) is the single most important viral respiratory pathogen of calves causing high morbidity and mortality in the European cattle industry. The extensive use of antibiotics to control secondary infections following BRSV increases the likelihood of the emergence of antibiotic-resistant bacteria. Consequently, the impact of BRSV on economics, animal welfare and public health makes the control of this virus a high priority. To control BRSV, sanitary measures need to be combined with effective vaccination. However, current vaccines are unsatisfactory, especially in young calves with maternally derived antibodies (MDA). Three of the project partners (P1, P2 and P3) are developing and evaluating novel BRSV vaccines. P1 works on BRSV Immunostimulating Complexes (BRSV-ISCOMs), P2 on nanoparticles of RSV nucleoprotein subunits (N nanorings) and P3 on mucosal delivery of a live attenuated, genetically modified BRSV (rBRSV mutants). These approaches all enable the development of a test for differentiation of infected from vaccinated animals (DIVA), a field of expertise of Partner 4 (P4). The project aims are to ameliorate and compare the three BRSV vaccine candidates; and to identify the safest and most efficient vaccine protocol that will induce early, long-lasting clinical and virological protection. This approach will be compatible with large scale use and will have a DIVA characteristic. This can only be achieved by combining the skills of the 4 partners through a strong collaboration, including extensive student/scientist exchanges. To reach our goals, 4 work packages (WP) have been designed: In WP1, the vaccines of P1 and P2 will be improved and new subunit vaccines will be generated. Selected recombinant BRSV proteins will be produced and incorporated into ISCOMs, and N nanorings will be decorated with B cell epitopes from BRSV surface glycoproteins. The immunogenicity of these vaccines will be evaluated and optimised in mice and lambs. In WP2, the two subunit vaccines and a rBRSV mutant will be evaluated in a challenge model in calves with BRSV-specific MDA. To ensure optimal quality data and synergistic evolution of skills, the challenge model, as well as clinical, immunological and virological methods, will be transferred and standardised between P1, P2 and P3. In WP3, the duration of protection induced by two most effective vaccines identified in WP2 and a heterologous prime/boost vaccine combination, optimised in lambs, will be compared in MHC-defined calves with BRSV-specific MDA. The use of MHC-defined calves will allow a more detailed analysis of T-cell priming by the various vaccines. In WP4 DIVA tests will be developed and evaluated. This project will enable identification of the most appropriate vaccine to control BRSV infection. The DIVA approach will allow vaccine evaluation in the field and sero-epidemiological investigations. It will also provide key tools for any future control programme."
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