The Use of Irradiated Vaccines in the Control of Infectious Transboundary Diseases of Livestock

Vaccination has been one of the greatest achievements of mankind in enabling the eradication of serious, life-threatening diseases of man and his domesticated livestock. Many of the vaccines used today rely on technologies developed over 100 years ago involving some form of attenuation, i.e. the use of an alternative or mutant strain of a pathogenic organism that has reduced virulence whilst maintaining immunogenicity, or inactivation, where chemical or physical methods are used to kill virulent pathogenic strains. Such vaccines have been extremely successful in protecting against diseases caused by viruses and bacteria in both animals and man. Amongst the success stories where control has been achieved can be included smallpox and Rinderpest, two diseases that had a global impact, but have now been eradicated.

Apart from their efficacy in improving animal health and productivity, vaccines can have another significant impact in a society that increasingly demands accountability from the farmer and food processor in relation to the livestock products they market. Regulatory agencies demand a reduction in the residues of veterinary pharmaceuticals in the food chain, and the use of antibiotics, or coccidiostats, has been severely curtailed in production systems in the EU. Also, as the vaccinated animals’ well-being is enhanced, the animal welfare lobby can be more readily appeased when intensive production methods are employed. Although the potential returns from veterinary vaccines is lower than that from human (even FMD vaccines enjoy a low market uptake) their importance will grow in the future as the need to increase productivity and livestock resources in the developing world to feed a growing population requires more effective control of emerging transboundary diseases (TBDs). For viral diseases this will be most important since there are only a few antiviral agents available and vaccination is the only effective way to avert infection. Although some conventional live and attenuated viral and bacterial vaccines are available not all livestock infectious diseases are covered and attempts are being made to develop subunit vaccines, live viral vector vaccines, DNA vaccines and gene-deleted vaccines.

Parasitic infections, including tick-borne diseases, animal trypanosomoses, and helminthoses also have a significant impact on productivity, not always by causing overt, clinical disease, but by their insidious impact leading to poor growth, low calving and reduced milk yield. Historically, chemotherapeutic drugs have been the mainstay of treatment and control of diseases caused by animal parasites. They have been viewed as cheap, safe and effective, although of course they are required to be constantly administered to ensure animals will thrive. Their greatest drawback has been in the emergence of drug resistance that reduces their efficacy, or prevents their use; in contrast, there is no evidence that similar genetic adaptation to vaccine-induced immunity ever occurs. With protozoal infections, a few vaccines have been produced based mainly on live parasites that result in a low level infection that stimulates a protective immune response similar to that produced by the natural infection. These methods include vaccination with low doses of infective organisms (Eimeria), infections controlled by chemotherapy (Theileria parva), attenuated vaccines (Babesia, Theileria annulata) or truncated life cycles (Toxoplasma).

Multicellular helminth parasites such as trematodes (e.g. Fasciola, Schistosoma), nematodes (e.g. Haemonchus) and cestodes (e.g. Taenia) present an even greater challenge to the development of suitable vaccines since they are large, complex multicellular organisms that, unlike smaller organisms, cannot be internalised by the hosts’ phagocytic immune mechanisms, but instead stimulate allergic type immune responses and the recruitment of leucocytes, mast cells and eosinophils. Not surprisingly, few vaccines have been developed to protect against infections with helminth parasites. There is however one commercially available vaccine, against the lungworm Dictyocaulus viviparus, consisting of radiation-attenuated, infective L3 larvae. In spite of the problematic issues in the production, batch-to-batch variation, storage and distribution of a live vaccine it has been used successfully for 50 years.

Nevertheless, research to develop other irradiated vaccines was not seriously pursued for the past twenty years due to two main reasons; firstly it was considered that the development of technologies was impractical or impossible and secondly that modern subunit vaccines would provide a solution as they could be more easily developed. Twenty five years on from the advent of recombinant technology and in spite of improved understanding in immune effector mechanisms involved in generating host immunity there has been little advance in recombinant vaccines for parasitic diseases. There is now good reason to re-evaluate the use of irradiation attenuation for vaccine production. The recent successful development of an irradiated vaccine for human malaria has demonstrated anew the feasibility and practicalities of this technique and indicated that technical problems can be overcome using existing knowledge without recourse to sophisticated technology.

This CRP is proposed for five years.