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EIAV: News on the vaccine
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9th ICEID Abstracts / Journal of Equine Veterinary Science 32 (2012) S3-S95
Challenges and proposed solutions for more accurate serological diagnosis of equine infectious anemia C.J. Issel 1, M.T. Scicluna 2, S.J. Cook 1, R.F. Cook 1, A. Caprioli 2, I. Ricci 2, F. Rosone 2, J.K. Craigo 3, R.C. Montelaro 3, and G.L. Autorino 2 1 Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, KY, 2 Istituto Zooprofilattico Sperimentale delle Regioni Lazio e Toscana, Rome, Italy, 3 Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA
The serologic diagnosis of persistent infections with the equine lentivirus, equine infectious anemia virus (EIAV), is possible because equids produce antibodies against the major EIAV proteins when exposed to the virus. Since 1972, control programs for EIA based on serology have depended on the agar gel immunodiffusion (AGID) test which tests for antibodies against the major core protein (p26) of EIAV and, since the mid-1980s, a variety of enzyme linked immunosorbent assay (ELISA) test kits which also detect antibodies to the p26 antigen. This study documents the presence of EIAV genetic sequences in a number of persistently-infected horses and mules whose serums were interpreted as negative or equivocal on AGID tests but positive on ELISA tests and in immunoblot tests. The immunoblot test included antigens from a cell-adapted Wyoming strain of EIAV and has thus far proven effective in detecting antibodies against the 3 major proteins of EIAV (the surface unit gp90, the transmembrane gp45 and the major core p26) in samples from the across the US, Italy, and South American and Asian nations. Strategies designed to take advantage of the combined strengths of the ELISA and AGID tests were shown to be effective in limited studies in the US and are shown here to be effective in a national surveillance program for EIA in Italy. In the survey, 17% (25/149) of the equids considered to be infected with EIAV on combined comparative serologic data had reactions in the AGID test that were interpreted as negative or equivocal. These data document the benefits of using the three tiered laboratory system for the diagnosis of EIA, originally promulgated by the Committee on Infectious Diseases of Horses of the US Animal Health Association. The three tiers include ELISA-first testing, followed by confirmation of positives by AGID testing and, when needed, further testing by immunoblot for recognition of multiple EIAV antigens. Although the ELISA-first strategy introduces some confusing results, the discovery of up to 20% more cases of EIA makes it compelling. In our opinion, it is better and more defensible to find two samples in a thousand with resolvable but falsely-positive ELISA tests for EIA than to release two to three horses in ten thousand with falsely-negative test results for EIA (the rates seen in the Italian surveillance presented here). The data also illuminate the challenges for accurate diagnosis of EIA infections based on detection of virus/viral genetic sequences (RNA or DNA) or antibody detection alone.
EIAV: News on the vaccine C. Leroux UMR754 INRA University Lyon 1, Retrovirus and Comparative Pathology, Lyon 1 University, Lyon, France EIAV (Equine Infectious Anemia Virus) is a lentivirus, member of the retrovirus family and is related to HIV (Human Immunodeficiency Virus). EIAV infects horses and donkeys worldwide and is responsible for a persistent infection leading to a recurring disease classically characterized by clinical episodes associating fevers and thrombopenia. The recurring episodes are clearly associated with the emergence of new viral populations generated by mutation of the viral genomes able to temporary escape the host immune response. As with other retroviruses in humans and animals, the individuals remain infected for life and there is no cure available. Over the past three decades, efforts have been made to develop an efficient protective immune response by prophylactic vaccines able to protect horses against infection by homologous as well as heterologous EIAV strains. This review will focus on the “Chinese” and “American” strategies using either viral vaccine strains attenuated by successive passages in donkeys and donkey cells or genetically attenuated vaccines by suppression of viral genes. Their efficiencies go from exacerbation of clinical signs in vaccinated animals to protection against disease. Protection from heterologous strains remains a challenge. These developments are of importance in the context of animal health as well as models for HIV vaccines or against other retroviral infections.
Stability differences of envelope-specific T cells responses between newly EIAV infected and inaparent carrier horses C. Liu 1, S.J. Cook 1, J.K. Craigo 2, R.F. Cook 1, C.J. Issel 1, R.C. Montelaro 2, and D.W. Horohov 1 1 Maxwell Gluck Equine Research Center, University of Kentucky, Lexington, KY, 2 Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, Pennsylvania Unlike other lentiviruses, EIAV replication can be eventually controlled in most infected horses leading to an inapparent carrier state free of overt clinical signs. Maintenance of this carrier state is absolutely dependent on active immune responses as evidenced by the fact that immunosuppressive drugs can induce the recurrence of disease. However, the immune mechanisms that are responsible for this control of infection are not yet identified. As the resolution of the initial infection is correlated with the appearance of the virus specific CTL, it appears that cellular immune responses play an important role. However, most studies into this protective mechanism have been limited to the identification of specific epitopes, usually at a single time point in the infection. Few studies have examined the cellular immune responses to the viral antigens throughout
9th ICEID Abstracts / Journal of Equine Veterinary Science 32 (2012) S3-S95
Challenges and proposed solutions for more accurate serological diagnosis of equine infectious anemia C.J. Issel 1, M.T. Scicluna 2, S.J. Cook 1, R.F. Cook 1, A. Caprioli 2, I. Ricci 2, F. Rosone 2, J.K. Craigo 3, R.C. Montelaro 3, and G.L. Autorino 2 1 Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, KY, 2 Istituto Zooprofilattico Sperimentale delle Regioni Lazio e Toscana, Rome, Italy, 3 Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA
The serologic diagnosis of persistent infections with the equine lentivirus, equine infectious anemia virus (EIAV), is possible because equids produce antibodies against the major EIAV proteins when exposed to the virus. Since 1972, control programs for EIA based on serology have depended on the agar gel immunodiffusion (AGID) test which tests for antibodies against the major core protein (p26) of EIAV and, since the mid-1980s, a variety of enzyme linked immunosorbent assay (ELISA) test kits which also detect antibodies to the p26 antigen. This study documents the presence of EIAV genetic sequences in a number of persistently-infected horses and mules whose serums were interpreted as negative or equivocal on AGID tests but positive on ELISA tests and in immunoblot tests. The immunoblot test included antigens from a cell-adapted Wyoming strain of EIAV and has thus far proven effective in detecting antibodies against the 3 major proteins of EIAV (the surface unit gp90, the transmembrane gp45 and the major core p26) in samples from the across the US, Italy, and South American and Asian nations. Strategies designed to take advantage of the combined strengths of the ELISA and AGID tests were shown to be effective in limited studies in the US and are shown here to be effective in a national surveillance program for EIA in Italy. In the survey, 17% (25/149) of the equids considered to be infected with EIAV on combined comparative serologic data had reactions in the AGID test that were interpreted as negative or equivocal. These data document the benefits of using the three tiered laboratory system for the diagnosis of EIA, originally promulgated by the Committee on Infectious Diseases of Horses of the US Animal Health Association. The three tiers include ELISA-first testing, followed by confirmation of positives by AGID testing and, when needed, further testing by immunoblot for recognition of multiple EIAV antigens. Although the ELISA-first strategy introduces some confusing results, the discovery of up to 20% more cases of EIA makes it compelling. In our opinion, it is better and more defensible to find two samples in a thousand with resolvable but falsely-positive ELISA tests for EIA than to release two to three horses in ten thousand with falsely-negative test results for EIA (the rates seen in the Italian surveillance presented here). The data also illuminate the challenges for accurate diagnosis of EIA infections based on detection of virus/viral genetic sequences (RNA or DNA) or antibody detection alone.
EIAV: News on the vaccine C. Leroux UMR754 INRA University Lyon 1, Retrovirus and Comparative Pathology, Lyon 1 University, Lyon, France EIAV (Equine Infectious Anemia Virus) is a lentivirus, member of the retrovirus family and is related to HIV (Human Immunodeficiency Virus). EIAV infects horses and donkeys worldwide and is responsible for a persistent infection leading to a recurring disease classically characterized by clinical episodes associating fevers and thrombopenia. The recurring episodes are clearly associated with the emergence of new viral populations generated by mutation of the viral genomes able to temporary escape the host immune response. As with other retroviruses in humans and animals, the individuals remain infected for life and there is no cure available. Over the past three decades, efforts have been made to develop an efficient protective immune response by prophylactic vaccines able to protect horses against infection by homologous as well as heterologous EIAV strains. This review will focus on the “Chinese” and “American” strategies using either viral vaccine strains attenuated by successive passages in donkeys and donkey cells or genetically attenuated vaccines by suppression of viral genes. Their efficiencies go from exacerbation of clinical signs in vaccinated animals to protection against disease. Protection from heterologous strains remains a challenge. These developments are of importance in the context of animal health as well as models for HIV vaccines or against other retroviral infections.
Stability differences of envelope-specific T cells responses between newly EIAV infected and inaparent carrier horses C. Liu 1, S.J. Cook 1, J.K. Craigo 2, R.F. Cook 1, C.J. Issel 1, R.C. Montelaro 2, and D.W. Horohov 1 1 Maxwell Gluck Equine Research Center, University of Kentucky, Lexington, KY, 2 Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, Pennsylvania Unlike other lentiviruses, EIAV replication can be eventually controlled in most infected horses leading to an inapparent carrier state free of overt clinical signs. Maintenance of this carrier state is absolutely dependent on active immune responses as evidenced by the fact that immunosuppressive drugs can induce the recurrence of disease. However, the immune mechanisms that are responsible for this control of infection are not yet identified. As the resolution of the initial infection is correlated with the appearance of the virus specific CTL, it appears that cellular immune responses play an important role. However, most studies into this protective mechanism have been limited to the identification of specific epitopes, usually at a single time point in the infection. Few studies have examined the cellular immune responses to the viral antigens throughout