Infections with avian influenza virus (AIV) and Newcastle disease virus (NDV) can cause devastating losses to poultry producers. Outbreaks of avian influenza (AI) in poultry in Italy (1999-2000); Newcastle disease (ND) in chickens in Australia (1998-2000) and Mexico (2000); and ND in chickens and turkeys in Italy (2000) are the most recent examples of the severe losses from infection with virulent strains of these viruses. The highly virulent forms of AI and ND are reportable diseases because of the potential for devastating loss and rapid transmission. Consequently both diseases can impact international trade in poultry and poultry products. The source of most infections can be traced to contact with infected birds or from virus transferred by the movement of farm personnel or contaminated equipment. In contrast, the AI outbreak in Italy and the ND outbreak in Australia are believed to have been due to changes in endemic virus strains that were initially of low virulence but mutated to high virulence. Some AIV strains can also infect mammals, including humans as occurred in Hong Kong during 1997. Outbreaks of swine influenza have been linked to direct introduction from AIV strains. NDV can also infect humans but those infections are usually limited to conjunctivitis from accidental exposures such as aerosols of live vaccine or from rubbing the eyes with vaccine contaminated hands.
Central Asia is a region for transmission of influenza viruses and paramyxoviruses from Southeast Asia and China to Europe and from Russia and Europe to the Middle East, Israel and Africa. Migrating birds may transmit avian viruses every season because many of the migration flyways for birds are through the territory of Kazakstan and other Central Asia republics. Large epizootic outbreaks of influenza and NDV among the avian and animal populations in Kazakstan have been recorded on numerous occasions. Moreover, the territory of Kazakstan may be a reservoir for mutation and recombination of avian and swine influenza viruses and possibly for transfer of influenza viruses from animal population into human population. In Kazakstan, at the Institute of Microbiology and Virology there have been several instances of isolation of swine influenza viruses from human adults and children.
The isolation, characterization, and molecular analysis of new AIV and NDV in the Central Asia region and comparisons with other worldwide isolates are very important for understanding and controlling AI and ND both in Kazakstan and in USA. Information obtained from characterization of these new strains and their genes may be used for improvement of diagnostic reagents and vaccines.
The immunostimulating complex (ISCOM) delivery system extensively studied at the Institute of Microbiology and Virology is very attractive for creation of new vaccine preparations for both oral and intranasal immunization. This could be a potential vaccine vector for stimulation of strong humoral, mucosal and/or cellular immune responses with potential for cross-reactive protection. Moreover, ISCOMs may be a possible formulation for incorporation of different antigens into unique multivalent subunit vaccines.
The major objectives of the study are:
1. Isolation and serological identification of AIV and NDV strains that have been or are currently circulating in Central Asia.
2. Using sequencing and phylogenetic analysis of genes of AIV and NDV strains, determine the relatedness of Central Asian isolates to other worldwide viruses.
3. Extend phylogenetic data by sequence analysis of additional genes of isolated viruses.
4. Isolation of individual antigens of AIV and NDV using new MESK detergent and incorporation of isolated antigens
into ISCOM formulations.
5. Evaluation of immunogenic activity of selected ISCOM formulations (general humoral immunity, antibody isotype production and protection against disease and infection) in chickens and late stage embryos.
Participants:
The proposed project seeks to characterize central Asian isolates of avian influenza and Newcastle Disease viruses, to compare those isolates with others being identified world wide, and to evaluate ISCOM technology for enhanced protective immunity against avian viruses. The work will be carried out with the combined expertise of scientists from Institute of Microbiology and Virology and Agricultural Research Institute, Republic of Kazakstan, and the Southeast Poultry Research Laboratory, Agricultural Research Service, USDA in Athens, Georgia. Scientists from the Institute of Microbiology and Virology have access to current and historical central Asian viral isolates and have expertise in isolation and identification of AIVand NDV strains. They further have extensive expertise in isolation and purification of viral antigens, preparation of ISCOM formulations and evaluation of humoral and cellular immune response and evaluating the protection induced by different vaccine formulations in animal models. Scientists from the Agricultural Research Institute have extensive expertise and experience in isolation and characterization of avian influenza and NDV strains in Central Asia region, production of live and inactivated poultry vaccines and evaluation of vaccine preparations. Scientists at the Southeast Poultry Research Laboratory in Athens, GA have expertise in sequence analysis and phylogenetic analysis of AIV and NDV strains from many sites around the world. They also have expertise in novel vaccine development and evaluation of effectiveness of vaccines in both chickens and in embryos