BRSV and RSV translational model

BRSV

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.

Clinical readouts translation calf model for RSV

Symptoms

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.

Publications

Vaccination with recombinant modified vaccinia virus Ankara expressing bovine respiratory syncytial virus (bRSV) proteins protects calves against RSV challenge - Vaccine (2007)

Efficacy of a modified live intranasal bovine respiratory syncytial virus vaccine in 3-week-old calves experimentally challenged with BRSV - The Veterinary Journal (2007)

Kinetics of antiviral CD8 T cell responses during primary and post-vaccination secondary bovine respiratory syncytial virus infection - Vaccine (2006)

Restriction enzyme analysis of RT-PCR amplicons as a rapid method for detection of genetic diversity among bovine respiratory syncytial virus isolates - Veterinary Microbiology (2005)

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)

Antibody titer against bovine respiratory syncytial virus in colostrum-fed dairy calves born in various seasons. Am J Vet Res (1999)

Bovine herpesvirus 1 marker vaccines reduce the incidence of infections - Vaccine (1998)

Immune response of calves experimentally infected with non-cell-culture-passaged bovine respiratory syncytial virus - Arch Virol (1998)

Comparison of DNA application methods to reduce BRSV shedding in cattle - Vaccine (1998)

Serological indication for persisten­ce of bovine respira­tory syncytial virus in cattle and atempts to detect the virus - Arch Virol (1997)

Immunization of cattle with a BHV1 vector vaccine or a DNA vaccine both coding for the G protein of BRSV - Vaccine (1997)

Antibody responses against epitopes on the F protein of bovine respiratory syncytial virus differ in infected or vaccinated cattle - Archives of virology (1997)

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)

Experimental reproduction of respiratory disease in calves with non-cell-culture-passaged bovine respiratory syncytial virus - Veterinary quarterly (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)

A severe outbreak of respiratory tract disease associated with bovine respiratory syncytial virus probably enhanced by vaccination with modified live vaccine - Vet Q. (1989)

Development of a neutralising antibody response to an inoculated cytopathic strain of bovine virus diarrhoea virus - Vet Rec. (1989)

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)

Pathogenesis of naturally acquired bovine respiratory syncytial virus infection in calves: evidence for the involvement of complement and mast cell mediators - Am J Vet Res. (1989)

Pathogenesis of naturally acquired bovine respiratory syncytial virus infection in calves: morphologic and serologic findings - Am J Vet Res. (1989)

Analysis of the antibody response to bovine respiratory syncytial virus proteins in calves - J Gen Virol. (1989)

Ovine keratoconjunctivitis experimentally induced by instillation of Mycoplasma conjunctivae - Vet Q. (1988)

Epidemiological study of bovine respiratory syncytial virus infections in calves: influence of maternal antibodies on the outcome of disease - Vet Rec. (1988)

Isotype-specific ELISAs for the detection of antibodies to bovine respiratory syncytial virus - Res Vet Sci. (1987)

Immunoglobulin M-specific enzyme-linked immunosorbent assay for serodiagnosis of bovine respiratory syncytial virus infections - Am J Vet Res (1987)

Local and systemic antibody response to bovine respiratory syncytial virus infection and reinfection in calves with and without maternal antibodies - J Clin Microbiol. (1987)

Diagnosis of bovine respiratory syncytial virus infections improved by virus detection in lung lavage samples - Am J Vet Res (1986)