Project Manager
Tabynov Kaisar Kazybaevich
Academic degree, title: Candidate of Veterinary Sciences, Professor
Scopus Author ID: 55489111500
Researcher ID: J-4155-2015
ORCID: https://orcid.org/0000-0001-5823-1280
About the project
Relevance
An innovative project with an international collaboration aims to address the problem of specific prevention of highly pathogenic avian influenza (HPAI), which is causing enormous economic damage to the global poultry industry (the No. 1 source of protein in the human diet) and, at the same time, global food security. The problem is that currently used injectable vaccines against hPVD provide homologous protection, but have limited heterologous protection against ever-evolving field viruses due to the induction of inadequate levels of mucosal immunoglobulin A (IgA) and cellular immune response in the respiratory tract. In this direction, intranasal immunization is a promising method of influenza vaccination, which generates secretory IgA antibodies capable of blocking viral infection at the very approaches to the body (mucosal epithelial cells), and thus will provide not only protection against infection, but also against virus transmission. Importantly, mucosal immunity in influenza provides cross-protection not only against heterologous but also heterosubtypic viruses. Moreover, needle-free influenza vaccines offer superior logistical advantages over traditional parenteral vaccines, such as ease of administration and avoidance of biohazardous waste in the form of sharps. The choice of appropriate formulations is crucial for the successful administration of intranasal vaccines. In recent years, nanoparticle-based platforms have been used to develop intranasal vaccines, which are used not only as an antigen delivery system but also as an immunostimulatory component (adjuvant).
Project Objective
The aim of the project is to develop a new safe and effective intranasal vaccine against highly pathogenic avian influenza, where chitosan nanoparticles conjugated with mannose are used as a mucosal delivery system for the antigen of recombinant vaccine virus obtained by reverse genetics.
Expected and achieved results
Task 1: Analyze the protective efficacy of commercial influenza vaccines against epizootically relevant highly pathogenic avian influenza virus. Within the framework of this task, vaccines from different manufacturers, widely used in Kazakhstan and countries of the Eurasian Economic Union (Russia, Belarus, Kyrgyzstan, Armenia), will be comparatively experimentally tested for the ability to protect immunized birds from infection, transmission and death from the wild type of highly pathogenic avian influenza virus (HPAI) subtype H5N8 clade 2.3.4.4b, which is epizootically relevant for Kazakhstan and other countries of the world. This work is conditioned by the fact that in spite of mass immunization of livestock against HPAI at poultry farms of Kazakhstan, some of them still have cases of death and decrease in productivity of poultry from this infection. Therefore, an independent analysis of the protective efficacy of influenza vaccines is a demanded study that will provide valuable recommendations on this issue to the poultry industry, as well as to the authorized body in the field of veterinary medicine of Kazakhstan.
Task 2: Development and "Proof of concept" study of an intranasal nanovaccine against highly pathogenic avian influenza. For this purpose, a recombinant epizootically relevant epizootically relevant vaccine strain of influenza virus subtype H5N8 (clade 2.3.4.4b) will be constructed by reverse genetics and its residual virulence will be tested. Next, the vaccine virus will be accumulated under optimal culturing conditions in a sensitive biological system (chicken embryos or cell culture), inactivated by a chemical factor, purified and loaded into chitosan-mannose nanoparticles. The resulting nanovaccine formulation will be investigated for safety, immunogenicity and protective efficacy including protection against virus transmission in chickens under different immunization regimes (drug multiplicity and dose). Inactivated vaccine will be used as a comparison preparation. The nanovaccine with the most effective immunization regimen in birds will be used in further studies. It is known that combining different types of vaccines or methods of administration creates unique immune profiles in vaccinated individuals, and thus contribute to achieving higher efficacy from immunization. In this regard, the protective potential of an intranasal nanovaccine in a cross-immunization regimen of birds with an injectable inactivated vaccine will be evaluated. As a result of this work, the potential of intranasal nanovaccine as a primary or booster agent for inactivated HPV vaccines used in practice will be experimentally demonstrated for the first time.
Task 3: Experimental development in preparation of the vaccine for commercialization. Within the framework of this task, the duration of immunity in birds inoculated with the developed VPHP vaccine will be established, as well as the shelf life of the preparation under conditions of regime storage. In addition, draft regulatory documents will be prepared (Standard of the organization, Instructions for manufacturing and quality control and Guidelines for the use of the drug). The results of these works will allow to bring the development to NASA Technology Readiness Level 6 (TRL-6) according to the BIRAC scale for biotechnological field (veterinary medicine, vaccines), and thus increase the chances of attracting venture capital funding for further commercialization of this development.
List of publications (with references thereto) and patents
At least one (1) article or review will be published in a peer-reviewed scientific publication indexed in Science Citation Index Expanded and ranked in the 1st (first) or 2nd (second) quartile for impact factor in Web of Science and/or having a CiteScore percentile in Scopus of at least 65 (sixty-five), presumably in Frontiers in Veterinary Science [quartile 1(Q1);
https://www.frontiersin.org/journals/veterinary-science] or in another journal, and one invention application has been filed with the national patent office.
Information for potential users
The target consumers of the project results are poultry enterprises and the Ministry of Agriculture of the Republic of Kazakhstan, which annually purchase vaccines against BBVP for more than 1 billion tenge. Economic efficiency of the invested funds is very significant, as it allows to reduce by more than 20 times the state costs of compensating owners for fallen birds.
Members of the research group
Tabynov Kairat Kazybaevich
Academic degree, title: PhD, Associate Professor
Scopus Author ID: 57196167800
Researcher ID: N-8761-2017
ORCID: https://orcid.org/0000-0001-9411-7952
Karibaev Talgat Bolatovich
Scopus Author ID: 57200031011
Researcher ID: CXY-9183-2022
ORCID: https://orcid.org/0000-0003-4463-127X
Berdikulov Maksat Amanbekovich
Academic degree, title: Candidate of Veterinary Sciences
Scopus Author ID: 57218251998
Researcher ID: ELT-5385-2022
ORCID: https://orcid.org/0000-0003-1304-0354
Yelchibaeva Leyla Serikkalievna
Academic degree, title: Master of Veterinary Science
Scopus Author ID: 57563224400
Researcher ID: EGQ-1571-2022
ORCID: https://orcid.org/0000-0001-6895-7720
Zhusambayeva Slukyz Isagulovna
Academic degree, title: Candidate of Veterinary Sciences
Kuanyshbek Aidana
Academic degree, title: Master of Veterinary Medicine
Zharmambet Қuantay Қuanyshuly
Academic degree, title: 1st year master's student in veterinary medicine