Duration of immunity of a four-valent vaccine against bovine respiratory diseases

This study demonstrated the duration of immunity over 6 months of a vaccine against key bovine respiratory disease pathogens: Parainfluenza 3, Bovine Respiratory Syncytial Virus, Bovine Viral Diarrhoea and Mannheimia haemolytica. This was performed by challenge on colostrumdeprived calves at the age of 2 weeks. Recent European field isolates were used as challenge strains. Clinical signs and pathogen excretion or presence were monitored. Field relevance of the viral challenge strains was analysed using phylogenic analysis. Significant reduction of excretion of the 3 viruses in vaccinated animals was a consistent finding, demonstrating the efficacy of the vaccine. Reducing shedding is indeed key to interrupting the infection transmission chain and helping to achieve the protective effects of immunisation that extend beyond the individual. A significant reduction of clinical signs and lung lesions following the Mannheimia haemolytica challenge was also observed in vaccinated animals versus controls. Comparison of the challenge strains to an array of global and European strains, including recent ones, demonstrated a high genetic proximity, supporting the potential for the vaccine to maintain similar levels of efficacy in the field over a 6-month period post vaccination. Cattle, immunization, Parainfluenza 3, Bovine Respiratory Syncytial Virus, Bovine Viral Diarrhoea, Mannheimia haemolytica Bovine Respiratory Disease (BRD) is a multifactorial disease impacting cattle production. The disease is often referred to as a disease complex, involving both bacterial and viral pathogens as well as psychological (e.g. stress) and physical (e.g. air quality and temperature) factors in various combinations. It is recognized as having a major impact on the health and economics of beef and dairy production and is considered as the most important illness associated with feedlot cattle in the USA (Snowder et al. 2006) and possibly worldwide (Horwood et al. 2008). Bovine Respiratory Disease is a relatively common phenomenon in younger cattle, especially those housed in intensive conditions, with vaccination programmes against BRD commencing on some farms in calves as young as 2 weeks of age. The importance of the disease in young calves and growing animals requires the vaccines and programmes used from the outset to be as effective and appropriate as possible. The vaccine antigens being used need to be appropriate for the strains currently (and at risk of) circulating on farms. They also need to be presented efficiently to the vaccinated animal so as to ensure both an optimal primary vaccination course response and a long duration of protective immunity. The immuno-competence of vaccinated calves and the level of circulating maternally-derived colostral antibodies (MDA) present can also have an impact on the vaccination response. These factors and the specifics of the disease dynamics on farm are all important when determining the right vaccination approach. The study described herein provides an initial assessment of the relevance of the Bovalto Respi range of respiratory vaccines for the vaccination of young calves against four majors ACTA VET. BRNO 2017, 86: 325–332; https://doi.org/10.2754/avb201786040325 Address for correspondence: Corinne Philippe-Reversat Merial 29 avenue Tony Garnier 69007 Lyon, France Phone: +33 (0) 472 720 000 E-mail: corinne.philippe-reversat@merial.com http://actavet.vfu. cz/ BRD pathogens: Parainfluenza 3 (Pi3), Bovine Respiratory Syncytial Virus (BRSV), Bovine Viral Diarrhoea (BVD) and Mannheimia haemolytica (Mh). As per regulatory requirements, colostrum deprived calves were used, hence the study did not consider the relevance of and approaches for MDAs. This study confirms the efficacy of the antigens (type and presentation), the likelihood of significant duration of immunity being achievable from the vaccine (6 months) and discusses the relevance of the antigens used to current circulating pathogens in Europe. Four different vaccination-challenge studies were carried out to investigate the duration of immunity provided by Bovalto Respi 4® against each of the strains included in the vaccine, i.e. Pi3, BRSV, BVD, and Mannheimia haemolytica. The design was similar for each study, apart from the challenge materials themselves and the type of follow-up that was used (adapted to each pathogen). Materials and Methods Vaccine efficacy Efficacy requirements of the immunogenicity test of the corresponding European Pharmacopoeia (Ph. Eur.) monographs were applied when existing (or by default, monographs dealing with similar antigen were used). The consent of the Ethics Committee on the use of animals for the trial was obtained. Two-week-old colostrum deprived calves were vaccinated twice at 21-day intervals and challenged 6 months after the 2nd injection. Ten calves were used for the viral studies and divided into two groups, one of 5 vaccinated and one of 5 controls. Sixteen calves were used for Mannheimia haemolytica with groups of 8 each for the vaccinated animals and controls. Animals were observed daily during the 14 days after challenge for the viral strains in order to detect clinical symptoms of respiratory disease such as sneezing, nasal discharge, coughing, etc. A scoring table was used for each of the criteria. Rectal temperature was also recorded daily and temperatures above 40 °C were considered as hyperthermia. Nasal swabs were systematically performed, starting on the day of challenge and subsequently daily from the 3rd day post-challenge until the end of the study. The follow-up of calves challenged by Mannheimia haemolytica (M. haemolytica) was shorter, lasting just 7 days (as per Ph. Eur. 1944 recommendations for the immunogenicity test). Daily clinical observations for respiratory signs as well as rectal temperature were recorded. A post mortem examination was performed to identify lung lesions caused by M. haemolytica and to re-isolate the bacteria. Indeed, M. haemolytica is commensal in the upper respiratory tract, becoming pathogenic once it has reached the lungs where it causes severe pathology to lung tissue such as fibrinous changes and necrosis. Table 2 below recapitulates details on the challenge materials used in the vaccine efficacy studies (virus details and inoculation approach). Serology was performed on blood samples to determine the level of antibodies for the viral strains using virus neutralisation technique and results were expressed as PD50 (serum dilution protecting 50% of the infected wells). A classical enzyme-linked immunosorbent assay (ELISA) was performed to assess the level of M. haemolytica antibodies. Nasal swabs were immediately diluted and inoculated into MDBK cell line suspension on 96-well plates. After incubation for 5 days, Pi3 titre was determined based on its specific cytopathogenic effect whilst immunofluorescence staining was used to reveal and titrate the levels of BVD and BRSV. Results were expressed in TCID50 (50% Tissue Culture Infective Dose). In the course of M. haemolytica challenge, post mortem lungs samples were cultivated in a liquid medium in tubes. The positivity of the samples for M. haemolytica was then assessed. The level of difference between vaccinated and control groups was tested by comparison of two independent selections using the QC Expert 3.1 program and the significance level α = 0.05. First, the compliance of variances of both selections was tested by the Fisher-Snedecor test and based on the test results a matching t-test (for the same or different variances) was subsequently used for testing of the compliance of the mean values.