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Journal of Virology, March 2005, p. 2666-2677, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.2666-2677.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Discerning an Effective Balance between Equine Infectious Anemia Virus Attenuation and Vaccine Efficacy

Jodi K. Craigo,¹ Feng Li,¹ Jonathan D. Steckbeck,¹ Shannon Durkin,¹ Laryssa Howe,² Sheila J. Cook,³ Charles Issel,³ and Ronald C. Montelaro^1,2*

Department of Molecular Genetics and Biochemistry,¹ Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, Pennsylvania,² Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky³

Received 3 June 2004/ Accepted 8 October 2004

Among the diverse experimental vaccines evaluated in various animal lentivirus models, live attenuated vaccines have proven to be the most effective, thus providing an important model for examining critical immune correlates of protective vaccine immunity. We previously reported that an experimental live attenuated vaccine for equine infectious anemia virus (EIAV), based on mutation of the viral S2 accessory gene, elicited protection from detectable infection by virulent virus challenge (F. Li et al., J. Virol. 77:7244-7253, 2003). To better understand the critical components of EIAV vaccine efficacy, we examine here the relationship between the extent of virus attenuation, the maturation of host immune responses, and vaccine efficacy in a comparative study of three related attenuated EIAV proviral vaccine strains: the previously described EIAV_UKS2 derived from a virulent proviral clone, EIAV_UKS2/DU containing a second gene mutation in the virulent proviral clone, and EIAV_PRS2 derived from a reference avirulent proviral clone. Inoculations of parallel groups of eight horses resulted in relatively low levels of viral replication (average of 10² to 10³ RNA copies/ml) and a similar maturation of EIAV envelope-specific antibody responses as determined in quantitative and qualitative serological assays. However, experimental challenge of the experimentally immunized horses by our standard virulent EIAV_PV strain by using a low-dose multiple exposure protocol (three inoculations with 10 median horse infective doses, administered intravenously) revealed a marked difference in the protective efficacy of the various attenuated proviral vaccine strains that was evidently associated with the extent of vaccine virus attenuation, time of viral challenge, and the apparent maturation of virus-specific immunity.

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* Corresponding author. Mailing address: Department of Molecular Genetics and Biochemistry, W1144 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261. Phone: (412) 648-8869. Fax: (412) 383-8859. E-mail: rmont{at}pitt.edu.

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Journal of Virology, March 2005, p. 2666-2677, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.2666-2677.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• 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]