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

Closed for proposals

Project Type

Coordinated Research Project

Project Code

D32033

CRP

2132

Approved Date

5 October 2016

Status

Closed

Start Date

2 January 2017

Expected End Date

30 June 2022

Completed Date

11 March 2024

Participating Countries

Bangladesh
Egypt
Ethiopia
Germany
Iran (Islamic Republic of)
Italy
Sri Lanka
Sudan
Zimbabwe

Description

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.

Objectives

To develop processes and protocols for an optimal culture, irradiation attenuation, preservation and formulation of animal pathogens and to define parameters for their use as vaccines against infectious diseases in animals. To evaluate the capacity of irradiated viruses as immune inducers.

Specific objectives

Develop methods and SOPs for medium scale irradiation attenuating of Theileria spp., Fasciola spp , Haemonchus contortus, Pox viruses and Brucella and establish the optimal dose and best way of application.

Evaluate the cost benefits of radiation attenuated vaccines for Haemonchus contortus and F. gigantica

Evaluate the use of protective agents/ reagents during irradiation

Examine potential for enhancing production processes and improving the immunogenicity of LSD and Brucella vaccines by using radiation attenuation.

Develop a process for cryopreservation for irradiated pathogens and cells

Develop immunological tools and methods to evaluate the immune response of animals to irradiated vaccines

Evaluate the applicability of irradiated viruses as immune inducers and adjuvants in vaccines.

Impact

The CRP provided information on irradiation doses that are needed to safely inactivate pathogen while preserving their immunogenic epitopes. Thus, candidate vaccines were introduced; and they were tested for their immunogenicity and protection was induced upon challenge by specific pathogens. It was understood that irradiated vaccines could not only provide protection against the strain of pathogen that it was immunized against but also different strains of the same pathogen confirming cross-protection. Moreover, the possibility of delivering irradiated vaccines through mucosal routes and obtaining protection was also proved. Overall, the CRP produced 13 scientific publications appearing in high-impact journals and leading to 9 post graduate theses.
This novel information has provided a thrust for the research and development of the irradiated vaccines in the livestock industry.

Relevance

The candidate experimental vaccines developed within this CRP will aid to prevent and control livestock diseases leading to increased productivity, higher income for the farmers and better nutrition in member states. Thus it will help to achieve SDG 2, which aims to “end hunger, achieve food security and improved nutrition, and promote sustainable agriculture."

CRP Publications

Type

Journal Article

Year

2019

Publication URL

http://www.uni-sz.bg/bjvm/2019-0094%20OnFirst.pdf

Description

REDUCTION OF VIRAL LOAD OF AVIAN INFLUENZA A VIRUS (H9N2) ON SPF EGGS AND CELL LINE BY GAMMA IRRADIATION

Country/Organization

Bulgarian Journal of Veterinary Medicine

Type

Journal Article

Year

2021

Publication URL

http://jams.arakmu.ac.ir/article-1-6076-en.html

Description

Inactivation of Human Influenza Virus Using Gamma Irradiation

Country/Organization

Journal of Arak University Medical Sciences

Type

Journal Article

Year

2018

Publication URL

https://scialert.net/abstract/?doi=ajava.2018.324.331

Description

Molecular Characterization of Isolated Mannheimia haemolytica and Pasteurella multocida from Infected Sheep and Goats Using RAPD and ERIC Markers

Country/Organization

Asian Journal of Animal and Veterinary Advances

Type

Journal Article

Year

2022

Publication URL

https://www.frontiersin.org/articles/10.3389/fvets.2022.907369/full

Description

Improved Whole Gamma Irradiated Avian Influenza Subtype H9N2 Virus Vaccine Using Trehalose and Optimization of Vaccination Regime on Broiler Chicken

Country/Organization

Frontiers in Veterinary Science

Type

Journal Article

Year

2022

Publication URL

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210829/

Description

Evaluation of room temperature (30°C to 35°C) lyophilized vaccine with radio inactivated Mannheimia haemolytica whole cells isolated from infected sheep

Country/Organization

Veterinary World

Type

Journal Article

Year

2021

Publication URL

http://pvj.com.pk/pdf-files/41_2/306-308.pdf

Description

Mycoplasma gallisepticum Detection in Bangladesh Table Egg Laying Chicken Flocks

Country/Organization

Pakistan Veterinary Journal

Type

Journal Article

Year

2018

Publication URL

https://akjournals.com/view/journals/030/65/2/article-p163.xml

Description

Analysis of antigen conservation and inactivation of gamma-irradiated avian influenza virus subtype H9N2

Country/Organization

Acta Microbiologica et Immunologica Hungarica

Type

Journal Article

Year

2020

Publication URL

https://www.scielo.br/j/babt/a/WLZvBbyyWnyFYKrvg5C8kbC/?lang=en

Description

Evaluation of Immune Responses and Histopathological Effects against Gamma Irradiated Avian Influenza (Sub type H9N2) Vaccine on Broiler Chicken

Country/Organization

Brazilian Archives of Biology and Technology

Type

Journal Article

Year

2021

Publication URL

https://link.springer.com/article/10.1007/s00705-020-04900-3

Description

Protective cellular and mucosal immune responses following nasal administration of a whole gamma-irradiated influenza A (subtype H1N1) vaccine adjuvanted with interleukin-28B in a mouse model

Country/Organization

Archives of Virology

Type

Journal Article

Year

2020

Publication URL

https://www.ajol.info/index.php/evj/article/view/201461

Description

Immunogenicity and protective efficacy of irradiated Salmonella Gallinarum against homologous challenge infection in Bovans brown chickens

Country/Organization

Ethiopian Veterinary Journal

Type

Journal Article

Year

2022

Publication URL

https://www.frontiersin.org/articles/10.3389/fvets.2022.916108/full

Description

Protective Efficacy of H9N2 Avian Influenza Vaccines Inactivated by Ionizing Radiation Methods Administered by the Parenteral or Mucosal Routes

Country/Organization

Frontiers in Veterinary Science

Type

Journal Article

Year

2021

Publication URL

https://onlinelibrary.wiley.com/doi/10.1002/vms3.680

Description

Carboxymethyl chitosan bounded iron oxide nanoparticles and gamma-irradiated avian influenza subtype H9N2 vaccine to development of immunity on mouse and chicken

Country/Organization

Veterinary Medicine and Science

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