Story Irradiated Vaccines - IAEA

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Animals in general possess a basic defense against pathogens known as innate immunity. This comprises two parts: (i) humoral, referring to substances found in body fluids such as tears, mucus and blood that can prevent the development of pathogens so that they can be eliminated from the body and (ii) cellular, where cells called phagocytes ingest pathogens. Irradiated vaccines and the control of animal diseases The first contact the immune system has with an infectious agent generates a primary immune response that results in the development of memory cells. These will respond to a second exposure to the same antigen by inducing a secondary immune response that is stronger and more effective than the primary one. Active immunity is developed following exposure to a pathogen but can also be induced artificially by vaccination, which requires the pathogen to be in a form that provokes an immune response without causing the disease. The primary vaccination might be followed by booster doses to maintain a level of immunity that will continue to protect the individual against infection. presence of their residues in human food, emphasize the importance of seeking alternative methods of control. These facts provide a strong argument for developing vaccines wherever possible, especially for parasitic diseases, where long term drug treatment, with all its potential problems, might be the only way to prevent disease. Irradiated Trypanosoma brucei parasites have been used successfully to induce immunity in cattle. Vaccination is a very cost effective way of controlling disease. Bacterial and parasitic diseases can be controlled by antibiotics and chemotherapeutics, but these have their limitations as reinfection might still occur, so it may be necessary to continually treat animals. Additionally, the increased incidence of antibiotic and drug resistance, as well as the Ideally, a vaccine should be stable and easy to administer in the field. It should induce an effective immune response that will protect the animal and have a prolonged effect even after a single inoculation. Conventional vaccines fall into one of three types: (i) live, attenuated vaccines, (ii) killed, inactivated vaccines, and (iii) toxoids. Live vaccines are prepared from organisms that have no virulence in the target animal. They are prepared from naturally occurring or induced mutated organisms by culture passage to reduce their pathogenicity or by attenuation using irradiation. Killed vaccines are prepared from highly immunogenic strains of organisms that are treated with chemicals that do not interfere significantly with the conformation of their surface proteins. Toxoid vaccines are based on antigenically altered toxins that are secreted by the pathogen and produce the clinical symptoms associated with the disease. In this case, the vaccine does not prevent infection but protects against the effects of the toxins produced by the pathogen. The search for new vaccines has led to novel strategies including peptide vaccines, recombinant vector vaccines, gene-deleted vaccines, marker vaccines, DNA vaccines, synthetic vaccines and edible vaccines. However, the most successful vaccines have been those based on conventional attenuation procedures; for example, the eradication of rinderpest is due to the use of an attenuated tissue culture vaccine developed over 50 years ago. An attraction of live vaccines is their potency; although they are attenuated they still replicate and induce the host to secrete the immunoregulatory products and cellular activation responses that would occur in natural infection. This includes the ability to generate not just antibody responses that are effective against extracellular

Transcript of Story Irradiated Vaccines - IAEA

Page 1: Story Irradiated Vaccines - IAEA

Animals in general possess a basic defense against

pathogens known as innate immunity. This comprises two parts: (i) humoral, referring to substances found in body fluids such as tears, mucus and blood that can prevent the development of pathogens so that they can be eliminated from the body and (ii) cellular, where cells called phagocytes ingest pathogens.

Irradiated vaccines and the control of animal diseases

The first contact the immune system has with an infectious agent generates a primary immune response that results in the development of memory cells. These will respond to a second exposure to the same antigen by inducing a secondary immune response that is stronger and more effective than the primary one. Active immunity is developed following exposure to a pathogen but can also be induced artificially by vaccination, which requires the pathogen to be in a form that provokes an immune response without causing the disease. The primary vaccination might be followed by booster doses to maintain a level of immunity that will continue to protect the individual against infection.

presence of their residues in human food, emphasize the importance of seeking alternative methods of control. These facts provide a strong argument for developing vaccines wherever possible, especially for parasitic diseases, where long term drug treatment, with all its potential problems, might be the only way to prevent disease.

Irradiated Trypanosoma brucei parasites have been used successfully to induce immunity in cattle.

Vaccination is a very cost effective way of controlling disease. Bacterial and parasitic diseases can be controlled by antibiotics and chemotherapeutics, but these have their limitations as reinfection might still occur, so it may be necessary to continually treat animals. Additionally, the increased incidence of antibiotic and drug resistance, as well as the

Ideally, a vaccine should be stable and easy to administer in the field. It should induce an effective immune response that will protect the animal and have a prolonged effect even after a single inoculation. Conventional vaccines fall into one of three types: (i) live, attenuated vaccines, (ii) killed, inactivated vaccines, and (iii) toxoids. Live vaccines are prepared from organisms that have no virulence in the target animal. They are prepared from naturally occurring or induced mutated organisms by culture passage to reduce their pathogenicity or by attenuation using irradiation. Killed vaccines are prepared from highly immunogenic strains of organisms that are treated with chemicals that do not interfere significantly with the conformation of their surface proteins. Toxoid vaccines are based on antigenically altered toxins that are secreted by the pathogen and produce the clinical symptoms associated with the disease. In this case, the vaccine does not prevent infection but protects against the effects of the toxins produced by the pathogen.

The search for new vaccines has led to novel strategies including peptide vaccines, recombinant vector vaccines, gene-deleted vaccines, marker vaccines, DNA vaccines, synthetic vaccines and edible vaccines. However, the most successful vaccines have been those based on conventional attenuation procedures; for example, the eradication of rinderpest is due to the use of an attenuated tissue culture vaccine developed over 50 years ago. An attraction of live vaccines is their potency; although they are attenuated they still replicate and induce the host to secrete the immunoregulatory products and cellular activation responses that would occur in natural infection. This includes the ability to generate not just antibody responses that are effective against extracellular

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organisms but also the cellular immunity that is essential for killing intracellular organisms. Killed vaccines, in contrast, have a lower potency and sometimes require the inclusion of adjuvants, substances that assist in potentiating the immune response by acting as a slow release deposit for antigens at the site of injection.

there is potential for developing a vaccine for T. evansi, a species that shows a more limited antigenic diversity than the African tsetse-transmitted trypanosomoses.

The Animal Production and Health Section of the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture assists Member States to improve livestock productivity through the efficient use of locally available feed resources, adequate management practices, and efficient reproductive and breeding programmes, and helps in the development and transfer of proactive disease prevention and control measures using nuclear and nuclear-related technologies.

For more information please contact: Animal Production and Health Section IAEA Vienna International Centre, P.O. Box 100 1400 Vienna, Austria www.iaea.org

Our interest in this technology is due not only to the encouraging reports in the literature but also to the data generated in our own collaborative research project on ‘Veterinary Diagnosis and the Control of Rift Valley Fever’ and two technical cooperation projects in the Sudan on ‘Epidemiology and Control of Snail-Borne Diseases in Irrigated Areas’ dealing with fasciolosis and on ‘Characterization and Quality Assured Production of an Attenuated Theileria annulata Vaccine’. We need to focus our attention on specific issues, and our approach will be driven by the needs of our Member States in their goal to control major infectious transboundary diseases where there are no vaccines available, or where the vaccines are problematic such as for Rift Valley fever, contagious bovine pleuropneumonia, animal trypanosomoses, gastrointestinal helminths — the list is long. Already we know that irradiated sporozoites protect against infection with T. annulata; in trypanosomosis, we know just how few irradiated parasites are needed to induce strong

protective immune responses. This suggests that

There is scope under the concept of “One Health” to develop an irradiated vaccine for Schistosoma japonicum, a parasitic worm that affects some 40 species of wild and domestic animals, causing serious morbidity and mortality, and whose major impact lies in its ability to infect humans. Development of a veterinary vaccine would reduce the incidence of disease in cattle and buffalo, leading to a decline in the rate of zoonotic infection in humans, particularly in China.

Cross-bred zebu cattle in Africa suffering from

‘nagana’, a disease caused by several species of pathogenic trypanosomes.

It is appropriate that we look at vaccine technology and reconsider the potential for radiation attenuation as a technique that will enable us to produce vaccines that can measure up to the requirements of various regulatory bodies regarding their safety and potency. There is evidence, mainly accruing from work on Plasmodium falciparum (the parasite that causes malaria) and S. haematobium and S. mansoni (parasitic worms that infect humans), that radiation-attenuated sporozoites (the infective stages of the malaria parasite) and radiation-attenuated cercariae (the infective stages of the schistosome worm) deliver a high level of protection against parasites that, in natural infections, do not confer any degree of sterile immunity (or a slowly acquired immunity at best) upon the host. This suggests that irradiation, although the mechanism is unknown, increases the immunogenicity of the parasite. Alteration in gene expression is one possible way in which this enhanced immunogenicity might be brought about in Schistosoma, by altering the way the irradiated parasites pass through skin-draining lymph nodes and lungs, allowing prolonged priming of the immune system. Studies on Listeria have also shown that irradiated bacteria retain adjuvant and antigenic integrity that confer immunogenicity, whereas inactivation by heat treatment is ineffective.