Development and comparative evaluation of three new generation BRSV DIVA vaccines and a corresponding DIVA test

牛呼吸道合胞病毒（BRSV）是欧洲养牛业中引起犊牛高发病率和死亡率的唯一最重要的病毒性呼吸道病原体。广泛使用抗生素来控制BRSV后的继发感染增加了出现耐药性细菌的可能性。因此，BRSV对经济、动物福利和公共卫生的影响使控制该病毒成为高度优先事项。为了控制BRSV，卫生措施需要与有效的疫苗接种相结合。然而，目前的疫苗是不令人满意的，特别是在年轻的小牛与母源性抗体（MDA）。在本项目中，将评价三种新型BRSV疫苗，即BRSV免疫刺激复合物（BRSV-ISCOM）、RSV核蛋白亚基（N纳米环）和减毒活的转基因BRSV（rBRSV突变体），以确定最安全和最有效的疫苗方案，从而诱导针对BRSV的早期、持久的临床和病毒学保护。所有这三种疫苗方法都能够开发区分感染动物和接种动物的试验（DIVA）。这将有助于在实地进行疫苗评价和血清流行病学调查。它还将为未来的疾病控制计划提供一个关键工具。

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). In this project, three novel BRSV vaccines, BRSV Immunostimulating Complexes (BRSV-ISCOMs), RSV nucleoprotein subunits (N nanorings) and live attenuated, genetically modified BRSV (rBRSV mutants) will be evaluated to identify the safest and most efficient vaccine protocol that will induce early, long-lasting clinical and virological protection against BRSV. All three vaccine approaches enable the development of a test for differentiation of infected from vaccinated animals (DIVA). This will facilitate vaccine evaluation in the field and sero-epidemiological investigations. It will also provide a key tool for any future disease control progammes.