The Use of Irradiated Vaccines in the Control of Infectious Transboundary Diseases of Livestock (D3.20.29)

Rationale and background:

Vaccination has been one of the greatest achievements in enabling the eradication of life-threatening diseases of man and his domesticated livestock. Many of the vaccines rely on technologies requiring 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 the pathogens. Such vaccines have been extremely successful in protecting against diseases caused by viruses and bacteria in both animals and man. The need to increase productivity and livestock resources in the developing world to feed a growing population will require more effective control of emerging transboundary diseases (TBDs) and vaccines will continue to have an important role. For viral diseases there are only a few antiviral agents available and vaccination is the only effective way to avert infection. Although 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, trypanosomoses, and helminthoses also have a significant impact on productivity, leading to poor growth, low calving and reduced milk yield. Chemotherapeutic drugs have been the mainstay for the control of diseases caused by animal parasites. Their greatest drawback has been in the emergence of drug resistance that reduces efficacy, or prevents their use; in contrast, there is no evidence that similar genetic adaptation to vaccine-induced immunity ever occurs. Modern subunit vaccines were expected to provide a means to control parasitic diseases but, spite of the advances in recombinant technology and improved understanding of the immune effector mechanisms involved in generating host immunity, there has been little advance in development of recombinant vaccines.

An alternative technology that shows great promise is radiation attenuation; this has been shown to produce effective immunogens from viral and bacterial pathogens and also is effective for protozoal and helminth parasites, there is thus good reason to re-evaluate its use for vaccine production. The recent successful development of an irradiated vaccine for human malaria has demonstrated the feasibility and practicalities of this technique and indicated that technical problems can be overcome using existing knowledge without recourse to sophisticated technology.

Overall objectives:

The objective of this CRP is to develop protocols for the attenuation of animal pathogens and to define parameters for their use as vaccines against the causative agents of transboundary parasitic and other infectious diseases and to evaluate the effect of radiation on the potency of the irradiated products.

Specific research objectives:

  • Develop methods and Standard Operating Procedures (SOPs) for attenuating various parasitic organisms such as Trypanosoma evansi and T. vivax, Theileria spp., Fasciola hepatica and Schistosoma japonicum and bacterial and viral pathogens including, for example, Rift Valley Fever virus and Brucella and establish techniques for measuring the effectiveness and duration of vaccination to determine the potency of candidate vaccines.
  • Develop methods using isotope- and fluorescent-labelled parasites to enable tracking of parasites in vivo.
  • Expand preliminary studies on the irradiation attenuation of Schistosoma bovis and F. gigantica in by establishing requirements for the optimal attenuating radiation dose, numbers of parasites required for vaccination, methods for measuring immune responses (metabolic, egg counts, adult worm development) and examine possibility of developing a pilot manufacturing process.
  • Evaluate the cost benefits of radiation attenuated vaccines for parasitic and other infectious diseases.
  • Examine potential for enhancing production processes and improving the immunogenicity of vaccines by using radiation attenuation.
  • Develop a flow-through process for irradiating bacterial and viral agents.

Expected outputs:

  • Demonstration of the improved immunogenicity and protection of irradiated vaccines.
  • The migration and sequestration of parasites isotopically labelled with 75Se or red or green fluorescent protein traced in vivo in experimental animals.
  • Optimization of the radiation inactivation process confirmed by demonstration that pathogens maintain general metabolic activity and can initially establish in the skin or draining lymph nodes following inoculation but their progression to the bloodstream and other internal organs is compromised.
  • Protocols for radiation attenuation of different species of pathogenic organisms established and their efficacy as vaccine antigens confirmed by measurement of immune responses and resistance to challenge infection in vaccinated animals.
  • Pilot, small-scale vaccination production facilities and assessments made of vaccine efficacy in terms of immune protection and cost benefits of the vaccines.
  • Protocols and SOPS for preparation of parasitic, viral and bacterial attenuated vaccines.
  • A flow-through process for irradiating pathogens and increasing efficiency of vaccine production.

Implementation procedure:

Up to six research contracts will be awarded to Member States submitting appropriate research proposals aimed at achieving the research outcomes detailed in the proposal. For the submission, the Chief Scientific Investigator (CSI) will have to present his/her project with regard to the current equipment, human resources and experience levels available in his/her laboratory. Research Agreement holders will be invited to join the CRP and provide development support for radiation attenuation. Specific Technical Contracts will be awarded to support the CRP by examining aspect of radiation attenuation. The Animal Production and Health Laboratory (APHL) of the FAO/IAEA Laboratories at Seibersdorf will be involved in technical backup and providing reagents.

First Research Coordination Meeting (RCM)

The first RCM will be held in the latter part of 2010 after the award of Research Contracts and the Agreement Holders will also be invited to participate. The Agreement holders will provide an up-to-date briefing on current vaccine technologies and lyophilization techniques. The workplans will be presented by Research Contract holders, discussed by all participants and detailed plans drawn up for each one.

Programme of Work Following First RCM (Two years)

The work will proceed according to the defined workplans with the support of the CRP scientific officer. The focus will be on developing technologies for attenuation of several different pathogens. In view of the innovative scope of the research it will be essential that participants keep in contact with the CRP scientific officer on a regular basis, as exchange of information will be integral to the success of the CRP. By the end of this phase of the work, with the assistance of APHL, it is anticipated that validated techniques and SOPs for attenuation, for each of the pathogens will have been devised.

Second RCM

The second RCM will be held in 2012 to review the results of the first phase of the work. Discussions will include the possibility of publishing SOPs for irradiation and lyophilization and preparing detailed workplans for the next two years.

Programme of Work Following the Second RCM

The focus of this phase of the work will be on testing attenuated vaccines in experimental animals, including ruminants, to determine their efficacy in inducing immunity in relation to dosage, number of inoculations required and duration of protection in response to experimental and natural challenge. It is possible that some of the projects might be sufficiently advanced to organize small-scale manufacturing processes.

Final RCM 2014

The final RCM will be held in the middle of 2014 to review the findings of the CRP, with the results published in 2015 as an agency TECDOC or in an external, peer-reviewed publication.

Participants:

[Download pdf]

Reports:

  • Report of the First RCM, Vienna from 11 to 15 October 2010. [Download pdf]

Project Officer:

A. Diallo