Wageningen Bioveterinary Research (WBVR) conducts extensive research into the immunopathology of Bovine Respiratory Syncytial Virus (BRSV).
What is BRSV?
This virus is an important pathogen in cattle. It causes cold-like symptoms in adult animals, while in calves it infects the small airways, causing bronchiolitis or pneumonia. The virus causes outbreaks of this respiratory disease annually, particularly in calves up to the age of six months.
How does the virus spread?
Almost all cattle will have been infected with BRSV before their second year of life. Infections and re-infections mainly occur in the autumn and winter. Spreading of the virus is rarely seen at other times of the year, and the virus seems to survive in a dormant form within the population.
What are the symptoms?
BRSV can be particularly severe in young animals, where it often causes fever (body temperature above 39.5ºC), rapid breathing, breathing difficulties and abdominal breathing. The clinical symptoms usually start with coughing and nasal discharge. If the small airways are also affected, expiratory wheezing, rapid breathing and signs of shortness of breath, as well as cyanosis and forced breathing (active involvement of the rib and abdominal muscles on inhalation) are observed. Clinical symptoms coinciding with bronchiolitis and/or pneumonia are serious and are very likely to be fatal.
How do you control BRSV?
To control and prevent the disease, it is necessary to understand how the body ultimately protects itself against the virus. It is therefore important to know what the consequences of the infection are for the body and how the body's immune system reacts. After a natural infection or after vaccination, for example, virus-specific antibodies are produced as part of the specific immune system. An effective immune response means that the animal is protected against a potential (re)infection, but in some cases a non-effective immune response can also be induced. Plenty of cases are known in which, for example, infected vaccinated calves showed much more severe symptoms than unvaccinated ones. WBVR is conducting extensive research into the role of the immune system during the course of the clinical infection.
How does WBVR detect the virus?
Direct detection of virus in secretions from the airways using a PCR test is generally the fastest method of diagnosis. The virus can also be isolated from patient material (nasal/throat swabs, lung washes or lung tissue from autopsy). The patient material is then transferred to virus-sensitive cells, on which a characteristic abnormal effect can be observed after a few days to a week. Specific antibodies produced to combat the virus can be detected with an ELISA or virus neutralisation test (VNT).
Is a vaccine available?
Different types of vaccines are available: live/attenuated or inactivated virus vaccines, vaccines with one or more components and possible combinations (multiple components, live/attenuated and inactivated), all with vaccine-specific advantages and disadvantages. None of the current vaccines seems to be able to completely prevent an animal from becoming infected. As part of the CRO activities, WBVR offers a bovine RSV calf model that can be used to evaluate effectiveness of newly developed vaccines for the veterinary field.
Translational calf model for RSV
With our translational pre-clinical RSV model, new intervention strategies can be evaluated. In this model, calves are inoculated with the bovine variant of RSV (bRSV) resulting in a natural course of infection.
Bovine RSV is one of the main causes of respiratory disease in calves and is genetically highly related to human RSV. The clinical manifestation in calves is very similar to the situation in infants, which makes this large animal model of additional value to small animal models in which typical RSV-related disease is not induced.
The onset of illness is typically seen from 5 days post-challenge (dpc) starting with signs of an upper respiratory tract (URT) infection, including runny eyes and nose, and coughing. Following the course of infection, symptoms of the lower respiratory tract (LRT) develop, characterized by an increased breathing rate and/or laboured breathing and commonly accompanied with depression, inappetence and fever (usually peaking between 7 and 9 dpc).
Disease parameters in our calf model
The calf model offers unique opportunities to extensively assess the severity of respiratory disease by daily measurements and clinical observations, discriminating for general illness, URT and LRT disease.
- General illness is assessed by a severity score for activity and appetite and a measurement of body weight and rectal temperature.
- Assessment of URT disease includes a severity score for runny nose or eyes and cough.
- LRT disease is assessed by a severity score for effort of breathing, an actual count of the respiratory rate and measurement of oxygen saturation by pulse oximetry.
Evaluate intervention candidates
All disease parameters together provide a representative display of the clinical manifestation, which can be applied as a primary read-out to evaluate promising intervention candidates for their potential on clinical efficacy.
Human respiratory syncytial virus infection in the pre-clinical calf model
Local dornase alfa treatment reduces NETs-induced airway obstruction during severe RSV infection
Neutrophil extracellular traps cause airway obstruction during respiratory syncytial virus disease
Interleukin-9 polymorphism in infants with respiratory syncytial virus infection: a opposite effect in boys and girls.
Age-dependent differences in the pathogenesis of bovine respiratory syncytial virus infections related to the development of natural immunocompetence
Genetic susceptibility to respiratory syncytial virus bronchiolitis in preterm childeren is asosiated with airway remodeling genes and innate immune genes
Efficacy of a modified live intranasal bovine respiratory syncytial virus vaccine in three-week-old calves experimentally challenged with BRSV - The Journal of the British Cattle Veterinary Association (2005)
Bovine respiratory syncytial virus infection influences the impact of alpha 4- and beta(2)-integrin-mediated adhesion of peripheral blood neutrophils - Clinical and Experimental Immunology (2004)
Antonis, A.F.G.; Schrijver, R.S.; Daus, F.J.; Steverink, M.; Stockhofe, N.; Langedijk, J.P.; Most, R.G. van der (2003); Vaccine-induced immunopathology during bovine respiratory syncytial virus infection: exploring the parameters of pathogenesis; Journal of Virology 77 (22). - p. 12067 - 12073.
Airborne transmission of BHV1, BRSV, and BVDV among cattle is possible under experimental conditions - Veterinary microbiology (1999)
Antigenic and molecular analyses of the variability of bovine respiratory syncytial virus G glycoprotein; Journal of general virology (1997)
A quantitative investigation into outbreaks of bovine respiratory syncytial virus infections in cattle herds - American Journal of Veterinary Research (1996)
Experimental reproduction of respiratory disease in calves with non-cell-culture-passaged bovine respiratory syncytial virus - The Veterinary Quarterly (1996)
Antibody responses to the G and F protein of bovine respiratory syncytial virus after experimental and natural infections - Clin Diagn Lab Immunol (1996)
Type-specific serologic diagnosis of respiratory syncytial virus infection, based on a synthetic peptide of the attachment protein G - Journal of immunological methods (1996)
Subgrouping of bovine respiratory syncytial virus strains detected in lung tissue; Veterinary microbiology (1996)
Respiratory syncytial virus reinfections and decreased milk yield in dairy cattle - The Veterinary Quarterly (1995)
Bovine respiratory syncytial virus antibodies in sera of non-bovine species - Archives of Virology (1995)
Respiratory syncytial virus infections in human beings and in cattle, an epidemiological review - Journal of infection (1994)
Dynamics of bovine respiratory syncytial virus: a longitudinal epidemiological study in dairy herds - Archives of Virology (1993)
Immunity to human and bovine respiratory syncytial virus - Arch Virol. (1990)
Priming for local and systemic antibody memory responses to bovine respiratory syncytial virus: effect of amount of virus, virus replication, route of administration and maternal antibodies - Vet Immunol Immunopathol. (1989)
Activation of complement by bovine respiratory syncytial virus-infected cells - Vet Immunol Immunopathol. (1989)