Optimisation of the response to respiratory virus vaccines in cattle

COWS transfer antibody to their calves in colostrum. Although colostral antibody is critical for neonatal survival, it can interfere with endogenous antibody responses. This immunomodulation is significant when vaccination is integral to disease management (Kimman and others 1987). The inhibitory effect of maternally derived antibody on the endogenous immune response has been reported for bovine viral diarrhoea virus (Endsley and others 2003), bovine herpesvirus type 1 (BHV-1) (Bradshaw and Edwards 1996), bovine respiratory syncytial virus (BRSV) (Debouck and others 1994) and parainfluenza virus type 3 (PI3) (Marshall and Frank 1975). Other contributory factors include the dose of vaccine and site of administration, and the age (Siegrist and others 1998) and genetics (O’Neill and others 2006) of the recipient. Quantification of the inhibitory action of pre-existing (maternally derived) antibody on vaccine responses would allow better harmonisation of calf management and vaccination, while minimising non-responsiveness to vaccines and maximising herd immunity. This short communication describes a study to determine the threshold of pre-existing antibody below which vaccination against bovine respiratory viruses could be expected to induce a detectable antibody response in calves. The study population was the Robogen herd of HolsteinCharolais calves maintained at the Roslin Institute, Edinburgh (Young and others 2005). A total of 463 (244 male and 219 female) calves entered the study over four successive years. All the calves received approximately two litres of birth-dam colostrum within six hours of birth. Male calves had unrestricted suckling with their dams at grass, and female calves were weaned by 36 hours and raised indoors. At the start of sampling (day 0), the calves ranged from 60 to 167 days old. Blood samples were collected on days 0, 14, 28, 42, 63 and 77. On day 0, each calf received 2 ml of an attenuated BHV-1/ PI3 vaccine (Imuresp RP; Pfizer Animal Health), administered intranasally. On day 28, each calf received 2 ml of an attenuated BRSV vaccine (Rispoval RS; Pfizer Animal Health), administered intramuscularly; the calves received a second intramuscular dose of 2 ml of this vaccine on day 49. All the vaccinations were given in accordance with the manufacturer’s recommendations. The serum immunoglobulin G (IgG) responses to BHV1 were weak, and excluded from further analysis. The sera were tested by commercial ELISA for total BRSV/IgG (Svanovir BRSV-Ab; Svanova Biotech) and total PI3/IgG (Svanovir PIV3Ab; Svanova Biotech). Samples were tested in duplicate at a dilution of 1:25, using kit conjugate, and optical densities were read at 450 nm. The results were expressed as relative optical density (ROD) percentages compared with a common, strongly positive control. The mean (se) ROD for BRSV IgG on day 0 was 13·8 (20·4) per cent, and for PI3 IgG it was 39·6 (32·9) per cent. The changes (Δ) in antibody levels between the day of vaccination (day 0 or day 28) and days 14, 28, 42, 63 and 77 postvaccination were calculated for all the results. To facilitate regression analysis, all the ROD datasets were normalised by loge transformation. Antibody levels specific to both BRSV and PI3 were determined independently by Biobest Laboratories, using the serum neutralisation test (SNT). For each virus, a representative panel of 30 sera was analysed by SNT, and the relationship with the corresponding ELISA results was evaluated. Using linear regression, equations were developed for both vaccines, linking the SNT titres [~1/X] to the respective ELISA results