High Mortality Rate Associated with Bovine Respiratory Syncytial Virus (BRSV) Infection in Belgian White Blue Calves Previously Vaccinated with an Inactivated BRSV Vaccine

Abstract

In a group of 60 Belgian White Blue calves less than 8 months old still housed in barns, a bovine respiratory syncytial virus (BRSV) outbreak was revealed on the basis of a direct diagnosis (immunofluorescence and virus isolation) performed on the lungs of dead animals, and the kinetics of BRSV neutralizing antibodies. Clinical signs, macroscopical and microscopical pulmonary lesions were also compatible with a BRSV infection. This outbreak is peculiar because the 35 oldest calves (204 +/- 29 days old) had been vaccinated 3-4 months before with an inactivated BRSV vaccine and 30% of these animals had died of respiratory distress. While they experienced a mild respiratory symptomatology, no death was recorded among the 25 youngest calves (69 +/- 29 days old) which had been left unvaccinated. Another peculiarity was found at the histological level where a massive infiltration of eosinophils was demonstrated in the pulmonary tissues of the dead animals. Together these data parallel the dramatic story described 30 years ago in children previously vaccinated with a formalin-inactivated human RSV (HRSV) vaccine upon a natural HRSV challenge. This illustrates that an immunopathological phenomenon also takes place after BRSV vaccination in cattle.

Bovine respiratory syncytial virus infection

“…Although virus shedding has occasionally been detected upon experimental BRSV re-infection, little or no clinical disease is observed in reinfected animals [69,109,134,145]. Similar to observations made for HRSV [67], exacerbated clinical signs have been observed following a natural BRSV infection in animals immunised with inactivated vaccines [5, 47,119].…”

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

“…Both with respect to epidemiology and pathogenesis, bRSV infection in calves closely resembles hRSV infection in infants and bRSV therefore, provides a valuable animal model for hRSV [1]. Vaccine development has been hampered by the fact that immunization with formalin-inactivated (FI) virus primes for a much more severe, and sometimes even lethal, form of respiratory disease [2][3][4][5][6]. This phenomenon was first observed in a human vaccine trial in the 1960s [4] and was later found to also occur in cattle immunized with formalin-or beta-propriolactone-inactivated bRSV [5,6].…”

“…Vaccine development has been hampered by the fact that immunization with formalin-inactivated (FI) virus primes for a much more severe, and sometimes even lethal, form of respiratory disease [2][3][4][5][6]. This phenomenon was first observed in a human vaccine trial in the 1960s [4] and was later found to also occur in cattle immunized with formalin-or beta-propriolactone-inactivated bRSV [5,6]. Enhanced disease resulting from immunization with Fl-virus has an immunopathological basis and has now been modeled in hRSV-infected mice [2,[7][8][9] and monkeys [10] and in bRSV-infected cattle [1,[11][12][13].…”

Antibody responses in mice after immunization with inactivated bovine respiratory syncytial virus using different adjuvants

“…BRSV vaccine failure events are reported both in scientific literature (SCHREIBER et al, 2000;LARSEN et al, 2001) and clinical evidence are observed by field veterinarians. On the present study, water-inmineral-oil emulsions (W/O), which is widely recognized as a potent adjuvant for use in farm animals, showed the best results when compared to any other treatments used, and it was included on the present research to serve as a "gold standard" for comparison with the other treatments.…”

“…Vaccines have Ciência Rural, v.40, n.11, nov, 2010. been used at least for the last 30 years to control BRSV infections in cattle (KERKHOFS et al, 2004;LETELLIER et al, 2008) and nowadays there are a number of commercially available BRSV vaccines (ELLIS et al, 1995;HÄGGLUND et al, 2004); whose use is controversial since its efficacy and potential enhancement of disease in vaccinated animals are not well documented under field conditions (SCHREIBER et al, 2000;LARSEN et al, 2001). Experimental assays using Modified-life virus (MLV) or inactivated vaccines (ELLIS et al, 1995(ELLIS et al, , 2005 showed different degrees of protection against pulmonary pathology induced by the challenge as well as production of neutralizing and non-neutralizing antibodies to BRSV, on the dependence of the type of vaccine and adjuvant used (ELLIS et al, 2001(ELLIS et al, , 2005.…”