By: Dr Grant van Lelyveld (BVSc.) Technical and Marketing Manager for Ruminants HIPRA Southern Africa (Pty) Ltd.
Why do we vaccinate our herds against diseases like Bovine Viral Diarrhoea (BVD), Infectious Bovine Rhinotracheitis (IBR), Quarter evil (Clostridial spp.) and other such things, but more importantly how can we ensure that we get the best results from the vaccines at our disposal?
The question can be answered as follows:
Firstly we vaccinate our animals to elicit an immune response (immunise), which is necessary to aid in the control and mitigation of disease. By immunising our animals we as veterinarians and farmers are aiding our animals to overcome certain challenges from the ever intensifying production systems we raise them in. Thus vaccination and immunisation is done to prevent and reduce the spread and erosive effects of the pathogens that affect the respiratory, reproductive, gastrointestinal systems, etc. that induce diseases at the individual and herd levels. By vaccinating the animals we are priming the immune system, to respond quicker to the actual problem and limiting the secondary consequences seen when naïve animals are challenged by a field/infectious pathogen. If we can speed up this process in a safe manner and not induce disease symptoms, we have achieved our goal. The development of immunity can take as long as 14 days to develop and through vaccination our animals are at an advantage because they do not need to rely on a process that has a time lag and also limits the negative effects experienced with infection e.g. energy loss taken away from production. Therefore through immunisation we build up the Adaptive/Acquired Immunity [cellular and humoral response (antibodies, T cells, etc.)] meaning that we do not just rely on the Innate Immunity [physical barriers (skin, mucosa, tears, etc.) and the cellular inflammatory response, which may be quickly responsive (immediate or within hours)] of the animal to protect the animal. By controlling the immunisation status of the individual animal and the herd, we are adhering to the principles of herd health and prevention which is the direction the animal health sector is moving. Thus we vaccinate and immunise our herds to limit financial losses and reduce additional expenses incurred when just the ambulatory approach is used to treat the infected and sick animals. This is a big focus for the future especially with the concerns around the misuse of antibiotics and the ever increasing resistance against antibiotics.
There is a twofold effect when prevention through vaccination/immunisation is used, because the focus is not just placed on protecting the individual animal directly, but by protecting the individual animal indirectly through lowering the pathogen load in the environment and increasing the immunity of the herd. This is because the direct protection depends on how well the individual animal responds to developing its own immunity, as each animal reacts in a set sequence (recognition of potential danger, the cascade of inflammatory chemokines and cytokines, the migration of cells associated with inflammation, which then moves into the development and multiplication of memory cells and antibodies to combat the infection as depicted by fig. 1 , but more importantly the strength of immunity induced depends on a multitude of factors e.g. concurrent infection, stress levels, etc. influencing the ability of the individual to build immunity. This is why vaccines are not 100% effective, and some animals will just not respond at all to the immunisation process. Therefore by vaccinating the herd we hope to induce a herd immunity that provides a protection level in which about 80% of the herd has responded on an individual level to protect the animals that may not have responded as desired. The direct and indirect immunity is further driven by using annual vaccination and immunisation to pick up some of the animals that did not respond, but also to increase the waning titre levels of the individual animals and that of the herd as a whole. This then has an accumulative effect.
Fig 1. The flow diagram of the development of the active immune system after the innate immune system has been primed with an antigen.
In this way vaccination plays a role in the Biosecurity of the farm. Vaccination then should be complemented by proper diagnostics, management, treatment and monitoring of the herd status (disease free, closed, etc.). By providing a safer environment through vaccination/immunisation we ensure that all stages of production (Foetus, Calf, Cow and Bull) on the farm are protected. This puts another focus on the importance of immunisation, because if we fail at one level we could have a negative effect at another level e.g. failure of passive immunity in the calves and the development of PI animals or abortions due to BVD and/or IBR.
Secondly there are some diseases that need to be vaccinated against, for legal reasons e.g. Rift Valley Fever and Brucellosis. This is because we need to protect the consumers and the farm staff from Zoonotic diseases, by providing a safe, sound and wholesome product and safe working environment. This can even go to a national level for the disease status of the country, affecting international trade due to the enforcement of regulations against the exportation of animal products or by-products e.g. Blue Tongue.
Table 1. Modelled outcome of 4 treatment scenarios in control and herds vaccinated with Starvac
Finally we vaccinate, because it is better to prevent than it is to cure a disease. This is evident when we look at the economic losses. It is not just the decreased production and the production of poorer quality carcases or milk, but it is the losses due to the high costs of treatment measures and drugs, the loss of future stock and superior genetics, etc.. It is also the losses of not being able to grow a herd while maintaining a high standard for selection of replacement stock or achieving short and long term goals.
So the next step is to address how we can better support or improve the results wanted from the vaccines. This ties in with management of the farm, which comes from knowing where we are now and where we want to go to in the future. In other words the ability to efficiently collect relevant farm data (diagnostics, farm records, etc.) and analyse this data to make the most informed decision to address current problems and have a positive progression and improvement of production parameters and economics (increased profits and positive returns on investments of preventative tools like vaccines). This will vary from farm to farm, as a result of different levels of technology, veterinary input and current management practices being used.
The focus points are: Animal factors, Environmental factors, Vaccine factors and Disease factors. By managing and understanding the influences of each factor or the combination of factors we can formulate vaccination programmes and choose suitable vaccines that will best assist us in controlling the diseases on our farms. The following factors and many more all contribute to true vaccination failure, as well as the perception of vaccination failure. From the list below, it can be seen that some aspects are easier to manage than others, but by managing as many as we can, we in essence complement and boost the benefits of vaccination/immunisation and vice versa.
Animal factors: Nutritional status and body condition, age (maternal immunity interference), production status (pregnant, etc.), etc.
Environmental factors: Season, housing, stocking density, stress, transportation, etc.
Vaccine factors: Killed or Modified live vaccines, vaccination protocols (time and booster effect), vaccine interference with drugs, cold chains, site of application, antigenic properties and concentration, etc.
Disease factors: Concurrent disease, immune suppression, use of antibiotics, etc.
The relationship between these factors can be depicted by the relationship of management, vaccination and pathogen load summarised by a model depicting the benefits of concurrent implementation. The results shows the positive relationship of good management and vaccination under different scenarios of high and low prevalence of Staph. aureus in a herd. Table one illustrates this best in scenario D in which the persistence of Staph. aureus and the number of clinical cases caused by Staph. aureus decreases by nearly half with just vaccination and more than two thirds with both vaccination and management . This is because mastitis is a multifocal disease, but farmers and veterinarians could only really influence the external factors through management [hygiene of the environment, calibration of the milking machine, efficient and hygienic milking routines and the correct nutritional plane and balance of vitamins (A and E) and minerals (Se, Cu, Zn and Fe)] with only a limited control on the animal factors (immunity). With the recent introduction of the polyvalent mastitis vaccine (Staph. aureus and E. coli) the farmer and veterinarian are now able to enhance the animal factors, and this combination of vaccination and management makes it possible to combat the negative effects caused by bacteria like Staph. aureus and E. coli.  This could be extrapolated to the triad approach to controlling the eradication of Persistently Infected (PI) animals and the control of BVD within herds.
Graph 1. The antibody titers for BVD type 1 during the entire vaccination program from the study evaluating the difference in the booster effect between MLV and Killed vaccines. The Killed vaccine had a booster effect about two times that of the MLV.
So when we look at vaccine factors we need to vaccinate the right animals (healthy and in the correct body condition), at the right time (prior to high stress or risk periods e.g. Classic protocol for the mastitis vaccine to focus on E. coli mastitis: 45 days prior to calving, 10 days prior to calving and 52 days post calving) and use the right vaccination protocol depending on the problem (calf morbidity/mortality or foetal/embryo losses e.g. vaccinating with a suitable BVD/IBR vaccine prior to breeding or prior to calving respectively). Nevertheless if we do not use or store the vaccine in the correct way, by maintaining a suitable stable cold chain or the correct mixing and administration of the vaccine as seen in the package inserts of the products we could be cancelling out the positive effects of the vaccine.
Graph 2. The antibody titers for BVD type 2 during the entire vaccination program from the study evaluating the difference in the booster effect between MLV and Killed vaccines. The Killed vaccine had a booster effect about two times that of the MLV.
A further aspect of the vaccine factor to consider is the type of vaccine: Killed or inactivated, Modified live (MLV) and live, as each vaccine type has its own strengths [e.g. Killed BVD/IBR vaccines have a management ease, proven safety in pregnant animals and versatility by addressing different problems in the different age groups (respiratory in calves and foetal protection in cows)] and limitations. A recent study conducted over a three year period has addressed one misconception about the short fall of Killed vaccines, and that is the strength and depth of the immunity induced by the use of Killed vaccines for BVD and IBR. The results from the study have shown that the immunity induced by Killed vaccines is in fact stronger than that of MLV, especially when it comes to the importance of the annual booster effect which is needed for the build up and continuous development of antibodies for the individual animal and herd immunity levels. Graphs 1, 2 and 3 and diagram 1 illustrate the results from the study which was conducted to build on the understanding of the reproductive protection achieved with the use of MLV or killed vaccines. From the results the higher levels of antibodies and immunity generated by the killed vaccines can be contributed to the fact that the immune system prevents the MLV antigens from multiplying efficiently which is needed to initiate and generate the antigenic mass necessary for the proper stimulation of the humoral response to increase antibody titre levels. This lack of antigenic mass does not occur in the killed vaccines due to two reasons, firstly the higher concentration of the inactivated antigens present in the vaccine and secondly the formulation of the adjuvants which primes the stimulation of the humoral response to be more efficient resulting in higher titre levels of antibodies to be achieved from the booster effect of the Killed vaccines. The higher levels of antibodies generated with the use of the Killed vaccine resulted in the reproductive benefit of a better foetal protection as none of the calves born from the Killed vaccine group aborted due to IBR or BVD and no PI calves were generated after the 16 day exposure of the whole herd with the 6 PI animals, as compared to the three abortions (one caused by BVD and two caused by IBR) and one PI calf from the MLV group. While all animals in the control group had a varying degree of reproductive problems caused by BVD and IBR (only four calves born alive of which all were PI animals and 11 abortions of which 7 were caused by both IBR and BVD, 3 caused just by BVD and one caused just by IBR). These reproductive failures all occurred at different stages in the gestation period . This has also been seen from a trial conducted in New Zealand and the results were discussed during the 2015 RUVASA congress. The results from this research also concluded that Killed vaccines have a good foetal protection with 87,5% of vaccinated animals not aborting due to BVD infection, 71,5% of calves born were PI free, even though the pregnant animals from the vaccinated and control groups were kept together with two PI animals from 118 days post AI and remained together for the remainder of the gestation .
Graph 3. The antibody titers for IBR (Bovine Herpes type 1) during the entire vaccination program from the study evaluating the difference in the booster effect between MLV and Killed vaccines. The Killed vaccine had a booster effect about four times that of the MLV.
The efficacy of a vaccine can also be affected by the type of active ingredient (virus, bacteria or toxin) and the adjuvant composition, as this affects the degree of immunisation, which is further influenced by the site (neck or rump) and method (I/M, I/V, S/C or intra nasal) of vaccination. There are many scientific trials that have been done to support vaccines and it is important to assess vaccines for additional benefits just over perceived cost of purchasing the vaccine. This is elaborated by the literature of several independent studies [4 and 6].
Diagram 1. The results of the reproductive protection from the trial has been tabulated for comparison of the MLV, Killed vaccine and no vaccination. The Results are depicted as abortion due to BVD, IBR or both as well as the development of PI calves after the exposure of the vaccinated and control groups to two PI positive animals.
I would like to close off by emphasising the importance of the following statement “We as farmers and veterinarians need to intensify and correctly use preventative tools like vaccines especially with the continuous intensification and growth of our farming systems, as we forget that the problems are bigger and more difficult to control, because we have not grown the preventative methods at the same rate as our farms.” Anonymous.
- Petzer, I., Karzis J. and Etter E., 2016. A model approach to estimate Staphylococcus aureus intramammary infection dynamics for different scenarios when vaccinating for mastitis. Published in the proceeding of the WBC, Dublin, Ireland.
- MacArthur, M and Casademunt, S., 2015. BVD foetal protection induced by vaccination in cattle. Published in the proceedings of the RUVASA congress, Western Cape.
- Walz P.H., et. al, 2017. Evaluation of reproductive protection against bovine viral diarrhea virus and bovine herpesvirus-1 afforded by annual revaccination with modified-live viral or combination modified-live/killed viral vaccines after primary vaccination with modified-live viral vaccine. Published by Elsevier. (Acquired through discussion).
- O’Toole D., Chase C.C.L., Miller M.M., and Van Campen H., 2014. Kennedy, the Early Sixties, and Visitation by the Angel of Death. Published in the Journal of Veterinary Pathology, Vol. 51(6) pages 1051-1062.
- Goldsby, Kindt & Osborne, 2000. Kuby Immunology fourth edition. Published by W. H. Freeman & Co. 41 Madison Avenue. City: New York. State: NY.
- Perry G.A., et. al, 2013. The effects of vaccination on serum hormone concentrations and conception rates in synchronized naive beef heifers.