Bovine respiratory syncytial virus ISCOMs-Immunity, protection and safety in young conventional calves.
Bovine respiratory syncytial virus ISCOMs-Immunity, protection and safety in young conventional calves.
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DOI：
10.1016/j.vaccine.2011.07.146
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发表时间：
2011-11-03
期刊：
影响因子：
5.5
通讯作者：
Valarcher JF
中科院分区：
文献类型：
--
作者：
Hägglund S;Hu K;Vargmar K;Poré L;Olofson AS;Blodörn K;Anderson J;Ahooghalandari P;Pringle J;Taylor G;Valarcher JF
► BRSV - ISCOMs在具有牛呼吸道合胞体病毒（BRSV）特异性母源抗体的常规小牛中诱导出强大的临床和病毒学保护作用。
► 这种保护作用与局部和全身性的体液免疫反应以及以干扰素γ产生为主的T细胞反应相关。
► 在攻毒后通过聚合酶链反应（PCR）或细胞培养未检测到病毒排出的动物，其肺部IgA水平特别高。
牛呼吸道合胞体病毒（BRSV）是牛毛细支气管炎和肺炎的主要病因，在欧洲每年都会引发高发病率的疫情。针对该病毒的商业疫苗需要提高效力，特别是在具有BRSV特异性母源抗体（MDA）的小牛中。我们之前报道过，一种实验性的BRSV - ISCOM疫苗（而非商业疫苗）在7 - 15周龄且具有MDA的小牛中诱导出强大的临床和病毒学保护作用。本研究的目的是描述免疫反应特征，并研究在更年幼动物（代表疫苗接种的目标群体）中的效力和安全性。四组每组五只3 - 8周龄且具有不同水平BRSV特异性MDA的小牛，以3周的间隔皮下接种两次，分别接种（i）BRSV免疫刺激复合物（BRSV - ISCOMs）、（ii）BRSV蛋白、（iii）佐剂或（iv）磷酸盐缓冲液（PBS）。所有小牛在2周后通过气溶胶方式接种强毒BRSV，并在感染后第6天实施安乐死。对攻毒后的细胞和体液免疫反应以及临床症状、病毒排出和病理变化进行监测。尽管在免疫接种时存在MDA，但在攻毒后，BRSV - ISCOM组仅观察到极少的临床症状。相比之下，在所有对照组中，大多数动物都出现了疾病的临床症状（呼吸频率高达76次/分钟，直肠温度高达41°C）。临床保护作用与小牛上呼吸道和下呼吸道中病毒复制的极显著减少、快速的全身性和局部抗体反应以及以干扰素γ产生为主的辅助性T细胞反应相关。在攻毒后通过PCR或细胞培养未检测到病毒排出的动物，其肺部IgA水平特别高。对BRSV蛋白的保护性免疫反应以及克服MDA抑制作用的能力取决于ISCOM所承载的抗原呈递。
► BRSV-ISCOMs induce strong clinical and virological protection in young conventional calves with BRSV-specific maternal antibodies. ► Protection is associated with local and systemic humoral responses as well as T cell responses dominated by IFNγ production. ► Animals that did not shed virus detectable by PCR or cell culture following challenge possessed particularly high levels of pulmonary IgA. Bovine respiratory syncytial virus (BRSV) is a major cause of bronchiolitis and pneumonia in cattle and causes yearly outbreaks with high morbidity in Europe. Commercial vaccines against this virus needs improvement of efficacy, especially in calves with BRSV-specific maternally derived antibodies (MDA). We previously reported that an experimental BRSV-ISCOM vaccine, but not a commercial vaccine, induced strong clinical and virological protection in calves with MDA, immunized at 7–15 weeks of age. The aim of the present study was to characterize the immune responses, as well as to investigate the efficacy and safety in younger animals, representing the target population for vaccination. Four groups of five 3–8 week old calves with variable levels of BRSV-specific MDA were immunized s.c. twice at a 3 weeks interval with (i) BRSV immunostimulating complexes (BRSV-ISCOMs), (ii) BRSV-protein, (iii) adjuvant, or (iv) PBS. All calves were challenged with virulent BRSV by aerosol 2 weeks later and euthanized on day 6 after infection. The cellular and humoral responses were monitored as well as the clinical signs, the viral excretion and the pathology following challenge. Despite presence of MDA at the time of the immunization, only a minimum of clinical signs were observed in the BRSV-ISCOM group after challenge. In contrast, in all control groups, clinical signs of disease were observed in most of the animals (respiratory rates up to 76 min−1 and rectal temperatures up to 41 °C). The clinical protection was associated to a highly significant reduction of virus replication in the upper and lower respiratory tract of calves, rapid systemic and local antibody responses and T helper cell responses dominated by IFNγ production. Animals that did not shed virus detectable by PCR or cell culture following challenge possessed particularly high levels of pulmonary IgA. The protective immunological responses to BRSV proteins and the ability to overcome the inhibiting effect of MDA were dependent on ISCOM borne antigen presentation.
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影响因子：
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