The Use of Nuclear Technologies to Fight Problem Diseases – the re-emergence of irradiated vaccines

Towards 2020 - New directions for the Animal Production and Health Subprogramme

The concept of vaccination is a sound one for the prevention of animal disease; fundamentally, it is designed to mimic the development of naturally acquired immunity by inoculation of non pathogenic, highly immunogenic organisms. Vaccines have an added advantage in that whilst having an impact on animal health and productivity they also enable reductions in veterinary pharmaceuticals in the food chain by eliminating the need for drugs or antibiotics to control disease. Vaccines may prevent clinical disease after infection, control disease at the herd level, or eradicate disease at the population level. Their impact is confirmed by the effectiveness demonstrated by the global elimination of rinderpest through vaccination. In the face of drug resistance, the emergence of new animal pathogens and the continuing lobbying of regulatory agencies to limit the use of pharmaceuticals (e.g. bans on antibiotics and coccidiostats) there is an urgent need to exploit all avenues in seeking to supplement methods for the control of animal disease. Vaccines account for about one quarter of the global market for animal health products, but nevertheless, there are still a number of major animal pathogens, including a number of transboundary diseases for which no vaccines are available, or for which the available vaccine is not considered sufficiently effective.

Amongst these diseases, some of the most intractable, are the human and animal trypanosomoses (Nagana). These infections threaten an estimated 60 million people and about 50 million head of cattle. Currently, between 50,000 and 70,000 people are estimated to be infected. Every year, Animal trypanosomiasis causes about three million deaths in cattle while approximately 35 million doses of trypanocidal drugs are administered. Nagana has a severe impact on agriculture in sub-Saharan Africa. The economic losses in cattle production alone are in the range of US$ 1.0 - 1.2 billion. For the total tsetse-infested lands total losses, in terms of agricultural Gross Domestic Product, have been put at US$ 4.75 billion per year.

Other diseases where there are no vaccines available or where the vaccines are problematic are Rift Valley fever, contagious bovine pleuro-pneumonia, peste de petits ruminants, capripox, theileriosis, ehrlichiosis, coccidiosis, anaplasmosis, fascioliosis and others as the list continues to grow. Malaria causes more than 300 million clinical cases and 1 million deaths and is responsible for the loss of more than 1% of the gross domestic product (GDP) in Africa and is a serious concern for locals, travellers and tourists. An effective vaccine in both the cases of Malaria and Trypanosomoses, could have made a dramatic impact on these diseases and the growth of agriculture in the continent of Africa. For 20 years, scientists have tried to develop modern, recombinant `subunit' trypanosome and malaria vaccines. This has been difficult. In fact, there is only one recombinant protein vaccine on the market for any disease, and no vaccines based on synthetic peptides, recombinant viruses, recombinant bacteria or DNA plasmids.

Most vaccines are based on attenuated or inactivated whole pathogens or chemically inactivated or sub-fractioned material derived directly from the infectious agent. The idea to use irradiated pathogens to mimic animal and human health pathogens are not new and documented in the literature since the early 1960s, in fact, the Animal Production and Health Subprogramme has been associated with this concept now for over 20 years. Despite the obvious advantages such as quality assured sterilization whist keeping the dimensional structure of the pathogens (i.e. it looks exactly like the infective pathogen but is dead or replicating deficient), good protection levels and reproducibility, this approach was not popular due to the use of a large radioactive cobalt source, the huge volumes involved and the inability to irradiate such volumes of infective pathogens and their subsequent freeze-drying, etc. The development of new equipment, decreases in input cost and the information generated within one of our CRPs (Veterinary diagnosis and control of Rift Valley fever) a TC project in the Sudan (Characterization and Quality-assured Production of an Attenuated Theileria annulata Vaccine)). This work and other data in the literature have brought the advantages and potential of irradiation to vaccinologist’s attention. It is a well established scientific fact that irradiated vaccines stimulate both arms of the immune response (i.e. the short and long term memory), along with their appropriate protection levels and the possibility to irradiate large volumes of pathogen containing fluid and to freeze-dry it in distribution aliquots (i.e. vaccine dose sizes) enable cost effective supply to the field without the constraints of required for handling attenuated, live vaccines and their physical dimensions.

The use of irradiation also has implications for currently applied technologies in use for Babesia ssp, where gamma irradiation of sera and red blood cells used in the live vaccine ensures freedom form contaminating IBR and BVD viruses. Of more fundamental interest are investigations on the transcriptome of irradiated helminth and trypanosome parasites that have revealed phenotypic changes that might account for the effectiveness of the immune responses stimulated by use of these attenuated organisms. Further investigations into this phenomenon might enable identification of specific genes involved in immunity. We at the Animal Production and Health Subprogramme, together with our Member States counterparts will address these issues as we see them as having significant benefit to our Member States and to our programme.