Abstract
BackgroundBovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease in cattle worldwide. Calves are particularly affected, even with low to moderate levels of BRSV-specific maternally derived antibodies (MDA). Available BRSV vaccines have suboptimal efficacy in calves with MDA, and published infection models in this target group are lacking in clinical expression. Here, we refine and characterize such a model.ResultsIn a first experiment, 2 groups of 3 calves with low levels of MDA were experimentally inoculated by inhalation of aerosolized BRSV, either: the Snook strain, passaged in gnotobiotic calves (BRSV-Snk), or isolate no. 9402022 Denmark, passaged in cell culture (BRSV-Dk). All calves developed clinical signs of respiratory disease and shed high titers of virus, but BRSV-Snk induced more severe disease, which was then reproduced in a second experiment in 5 calves with moderate levels of MDA. These 5 calves shed high titers of virus and developed severe clinical signs of disease and extensive macroscopic lung lesions (mean+/−SD, 48.3+/−12.0% of lung), with a pulmonary influx of inflammatory cells, characterized by interferon gamma secretion and a marked effect on lung function.ConclusionsWe present a BRSV-infection model, with consistently high clinical expression in young calves with low to moderate levels of BRSV-specific MDA, that may prove useful in studies into disease pathogenesis, or evaluations of vaccines and antivirals. Additionally, refined tools to assess the outcome of BRSV infection are described, including passive measurement of lung function and a refined system to score clinical signs of disease. Using this cognate host calf model might also provide answers to elusive questions about human RSV (HRSV), a major cause of morbidity in children worldwide.
Highlights
Bovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease in cattle worldwide
Our objective was to improve and characterize a BRSV model in calves, by selecting one of two inocula, based on two different strains passaged in calves or in cell culture, and used by two different research groups, to obtain a model that would induce clinical signs comparable to those observed in the field
Study 1: Evaluation of clinical, pathological and virological expression of two virulent BRSV inocula in calves with low levels of maternally derived antibodies (MDA) Clinical signs following challenge Following experimental infection, mild to severe clinical signs of respiratory disease were observed in all infected calves (Figure 1A)
Summary
Bovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease in cattle worldwide. Even with low to moderate levels of BRSV-specific maternally derived antibodies (MDA). Available BRSV vaccines have suboptimal efficacy in calves with MDA, and published infection models in this target group are lacking in clinical expression. Bovine respiratory syncytial virus (BRSV), a pneumovirus in the family Paramyxoviridae, is highly prevalent in cattle, with a significant economic impact as the most important viral cause of bovine respiratory disease (BRD) worldwide [1]. Most colostrum fed calves in endemic areas have BRSV-specific maternally derived antibodies (MDA) in serum, affording them limited protection from BRSV infection during the first weeks of life, but having a negative effect on the degree and duration of protection. Following vaccination, exacerbated reaction to natural or experimental infection, uncommon, has been described in calves [8,9], and resembles that previously observed in children immunized with an inactivated vaccine against the genetically and antigenically closely related pneumovirus, human RSV (HRSV) [10]
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