This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, F. Articles by Montelaro, R. C. Search for Related Content PubMed PubMed Citation Articles by Li, F. Articles by Montelaro, R. C.

A Live Attenuated Equine Infectious Anemia Virus Proviral Vaccine with a Modified S2 Gene Provides Protection from Detectable Infection by Intravenous Virulent Virus Challenge of Experimentally Inoculated Horses

Department of Molecular Genetics and Biochemistry,¹ Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261,² Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky 40516³

Received 3 January 2003/ Accepted 17 April 2003

Previous evaluations of inactivated whole-virus and envelope subunit vaccines to equine infectious anemia virus (EIAV) have revealed a broad spectrum of efficacy ranging from highly type-specific protection to severe enhancement of viral replication and disease in experimentally immunized equids. Among experimental animal lentivirus vaccines, immunizations with live attenuated viral strains have proven most effective, but the vaccine efficacy has been shown to be highly dependent on the nature and severity of the vaccine virus attenuation. We describe here for the first time the characterization of an experimental attenuated proviral vaccine, EIAV_UKS2, based on inactivation of the S2 accessory gene to down regulate in vivo replication without affecting in vitro growth properties. The results of these studies demonstrated that immunization with EIAV_UKS2 elicited mature virus-specific immune responses by 6 months and that this vaccine immunity provided protection from disease and detectable infection by intravenous challenge with a reference virulent biological clone, EIAV_PV. This level of protection was observed in each of the six experimental horses challenged with the reference virulent EIAV_PV by using a low-dose multiple-exposure protocol (three administrations of 10 median horse infectious doses [HID₅₀], intravenous) designed to mimic field exposures and in all three experimentally immunized ponies challenged intravenously with a single inoculation of 3,000 HID₅₀. In contrast, naïve equids subjected to the low- or high-dose challenge develop a detectable infection of challenge virus and acute disease within several weeks. Thus, these data demonstrate that the EIAV S2 gene provides an optimal site for modification to achieve the necessary balance between attenuation to suppress virulence and replication potential to sufficiently drive host immune responses to produce vaccine immunity to viral exposure.

This article has been cited by other articles:

• Tagmyer, T. L., Craigo, J. K., Cook, S. J., Even, D. L., Issel, C. J., Montelaro, R. C. (2008). Envelope Determinants of Equine Infectious Anemia Virus Vaccine Protection and the Effects of Sequence Variation on Immune Recognition. J. Virol. 82: 4052-4063 [Abstract] [Full Text]  
• Craigo, J. K., Zhang, B., Barnes, S., Tagmyer, T. L., Cook, S. J., Issel, C. J., Montelaro, R. C. (2007). Envelope variation as a primary determinant of lentiviral vaccine efficacy. Proc. Natl. Acad. Sci. USA 104: 15105-15110 [Abstract] [Full Text]  
• Tagmyer, T. L., Craigo, J. K., Cook, S. J., Issel, C. J., Montelaro, R. C. (2007). Envelope-specific T-helper and cytotoxic T-lymphocyte responses associated with protective immunity to equine infectious anemia virus. J. Gen. Virol. 88: 1324-1336 [Abstract] [Full Text]  
• Zhang, X., Wang, Y., Liang, H., Wei, L., Xiang, W., Shen, R., Shao, Y. (2007). Correlation between the induction of Th1 cytokines by an attenuated equine infectious anemia virus vaccine and protection against disease progression. J. Gen. Virol. 88: 998-1004 [Abstract] [Full Text]  
• Craigo, J. K., Li, F., Steckbeck, J. D., Durkin, S., Howe, L., Cook, S. J., Issel, C., Montelaro, R. C. (2005). Discerning an Effective Balance between Equine Infectious Anemia Virus Attenuation and Vaccine Efficacy. J. Virol. 79: 2666-2677 [Abstract] [Full Text]  
• Howe, L., Craigo, J. K., Issel, C. J., Montelaro, R. C. (2005). Specificity of serum neutralizing antibodies induced by transient immune suppression of inapparent carrier ponies infected with a neutralization-resistant equine infectious anemia virus envelope strain. J. Gen. Virol. 86: 139-149 [Abstract] [Full Text]  
• Jin, S., Issel, C. J., Montelaro, R. C. (2004). Serological Method Using Recombinant S2 Protein To Differentiate Equine Infectious Anemia Virus (EIAV)-Infected and EIAV-Vaccinated Horses. CVI 11: 1120-1129 [Abstract] [Full Text]