Irradiation of Transboundary Animal Disease (TAD) Pathogens as Vaccines and Immune Inducers

Vaccination has been one of the greatest achievements of mankind in enabling the eradication of serious, life-threatening human diseases and also of economically devastating diseases of livestock animals. Many of the vaccines used today rely on the technologies that has been developed over 100 years  which involves 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 both in animals and human. Two classic examples for this type of vaccines are smallpox and Rinderpest, two diseases that had a global impact, but have now been eradicated successfully. It is also noteworthy that vaccines by preventing the occurrence of diseases leads to reduced use of antibiotics and chemotherapeutics. The practice of extensive usage of antibiotics and chemotherapeutics specially in the animal production industry has rendered to the ineffective drugs(antibiotic resistance) and also leading to contaminants in food and environment, increasing the risks for allergies and other residual pathogens in aquatic environments.  Since the discovery of the first vaccine, a wide variety of research approaches were explored to design and develop vaccines for devastating diseases. Never the less many diseases that threatens human and animals still cannot be prevented through vaccinations. The promises of the biotechnology revolution did not deliver much and the recent approaches with vectored vaccines, i.e. utilizing one innocuous germ as the producer and vehicle for specific antigens of other disease agents have met with limitations in their immune response.Attenuation of pathogens was long the method of choice, if killed preparations did not deliver the desired immunity against the concerned pathogens. This process is very time consuming and reduction of pathogenicity can be observed in some cases only after passaging in animals or tissue cultures for more than 150 times.  Indeed, for certain pathogens as in parasites, this method is not applicable. As an alternative to classical methods,  by 1960s irradiation experiments were carried out to investigate their potential application for vaccine production. Unfortunately, these experiments had to be abandoned, after a decade of experiments, in the 1970s due to limitations in culture techniques, lack of molecular understanding of the genetics involved and of course rather limited irradiation sources. A renaissance of this approach was seen in the last 5 years due to newer irradiator technologies, better understanding of immunology and the with fine molecular approaches. Recent research reports show that cellular immune system can be fully stimulated only with a metabolically active pathogen. The genetic manipulation of pathogens to cripple their ability to multiply but still to enter a cell and produce metabolites to induce an immunity was not successful as in the case of virus like particles. This led to re-explore irradiation as a solution. It is possible to produce the pathogens in culture systems (most of the time) and subject to irradiation, causing random nicking of their genome thus losing the ability to replicate. As their surface structures are not altered they can still continue “living” in special media, but will not multiply in side the host when inoculated. This kind of approach became very popular in recent years, specially in tumour research. There are many economically devastating and zoonotic diseases in livestock for which there are no proven vaccines. Many of them, like the haemoparasites in Africa (trypanosomes, Theileria, Babesia, Anaplasma…) lead to endemic disease situation with enormous losses to farmers and of course to the society at large. Additionally, only a few immune stimulants for traditional attenuated vaccines (CBPP…) exist which leads to sub-optimal performances. Moreover, most of them are toxic for the live attenuated pathogens. In the recently completed CRP on irradiated vaccine development, a number of basic approaches could be experimentally tested and very promising results were obtained for certain pathogens for which there are no commercially available vaccines. However, many challenges in the expansion of production, formulation and storage of such vaccines became obvious. Also, experiments done to produce vaccines to some pathogens yielded sub-optimal results indicating the need for exploring novel strategies to obtain better results.  Therefore, the new CRP will explore novel approaches utilizing cutting edge immunological and molecular biological techniques to understand the effects of irradiation on pathogens and how it would induce the desired immunity and most importantly to prevent the occurrence of infection in the host. The CRP will also address the production process problems including preservation and formulation issues, develop immunological tools to proof protection (for instance for QA procedures) and will investigate the application of irradiated pathogens as immune inducers for use in other vaccines. This CRP is proposed for five years.