Project objective. Field tests for safety and effectiveness of new vector vaccine against cattle brucellosis in comparison with known commercial vaccine preparations (B. abortusS19, RB51).
Current situation in the given field of research. Currently, specific prophylaxis of bovine brucellosis is performed by using of live attenuated bacterial B. abortus S19 and RB 51 vaccines. It is known that these vaccines are highly effective but with number of serious disadvantages associated with their capability to cause abortion, virulence for humans and also formation of agglutinogens antibody (except RB 51 vaccine), which prevents subsequent differential diagnosis. Furthermore, the vaccine RB 51 is resistant to antibiotics such as rifampicin that is used to treat the disease. Therefore, the development and introduction in veterinary practice of safe and effective vaccine against bovine brucellosis which allowing differentiating infected animals from vaccinated animals today is the urgent problem.
To solve the problem of specific prophylaxis of bovine brucellosis, the RIBSP firstly proposed a completely new vaccine candidate based on the influenza viral vectors expressing Brucella ribosomal L7/L12 or Omp16 proteins. The developed vaccine according to the protective parameter (efficiency) is not inferior to the best in this regard commercial B. abortus S19 vaccine, and on the safety parameters significantly exceeds to all known commercial vaccines against bovine brucellosis (B. abortus S19, RB51). Another significant uniquely designed vaccine is that it is unlike the existing commercial preparations can be used in all age and sex groups of cattle, regardless of animals with pregnancy status, as in Brucella-free and Brucella-infected farms.
Impact of the proposed project on the progress in this field.
For application of the vaccine in veterinary practice of Kazakhstan it is necessary to demonstrate its safety and effectiveness in field trials in comparison with commercial vaccines. Positive results of the given trials will allow to use the vaccine as a highly efficient prophylactic preparation against brucellosis.
Competence of the project participants in this field.
Specialists of Microbiology and Infectious Disease Prevention labs of the RIBSP have a rich experience in the development, testing and introduction of preparations against various infectious diseases of farm animals and birds. This is evidenced by publications in such international editions as «Vaccine», «Virology journal», «Australian veterinary journal», «Ciencia rural» et al., as well as by reports at international conferences.
Expected results and their future application.
As a result of the project implementation is planned to organize and conduct a large-scale field trials of the developed vaccine safety and effectiveness in cattle (on the model of challenge study with virulent B. abortus 544 strain). The object of the study will be tested on different age and sex groups of animals, including pregnant animal in an amount sufficient to obtain objective data.
The results of the proposed project will be used as a basis for the developed vaccine further implementation to the production and its subsequent widespread use in veterinary practice.
Project relevance to the ISTC goals.
Despite of project participants with the knowledge in the field of weapons of mass destruction the given Project has only peaceful purposes thereby relevant to the ISTC goals. Also it is planned to involve scientists from the participant organizations into the international scientific community by providing information on the project at international conferences and seminars.
Data on the volume of work.
- Pilot production and quality control of cattle brucellosis vector vaccine;
- Preparation and quality assessment of a virulent B. abortus 544 strain, as well as of reference vaccines (B. abortus S19, RB51) for field trials;
- Organization, conducting and analysis of field trial results.
Technical approaches and methodology.
Currently, in Kazakhstan the procedure of industrial research of veterinary vaccines are regulated by the Rules of the veterinary preparations and feed additives approbation, approved by order of the Minister of Agriculture of the Republic of Kazakhstan dated November 24, 2014, № 7-1/611. In compiling the main objectives of the project we were guided by the specified rules.
The pilot production (not less than 100 000 doses/lot) vaccine will be carried out at the industrial site of the RIBSP which intended for the vaccines production based on egg technology. Quality control of the preparation will be conducted in accordance with approved in due order normative document.
Preparation and quality assessment of virulent B. abortus 544 strain, as well as of reference vaccines (B. abortus S19, 82, RB51) for field trials will be conducted using conventional bacteriological and serological techniques.
For testing the vaccine safety will be evaluated a general (general condition, behavior, appetite, temperature reaction, milk production) and local (presence of a tumescence at the injection site, and its diameter, duration of a tumescence resorption) reactions, identified in animals after vaccination. Additionally in pregnant cows during the period of observation will be evaluated the vaccine ability to cause abortions.
The vaccine protectiveness will be determined according to the normative document of preparation. For this purpose the animals of the vaccinated and control groups will be subjected to experimental challenge with virulent B. abortus 544 strain under ABSL-3 conditions. The vaccine protectiveness will be determined by the index of infected and number of Brucella allocated from tissues, and additionally assessed by the degree of protection against abortion.
Statistical analysis of the data received will be carried out with the help of «GraphpadPrismSoftware» program, version 6.0 (GraphpadSoftwareInc., CA, USA).
