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Journal of Virology, April 2008, p. 4052-4063, Vol. 82, No. 8
0022-538X/08/$08.00+0     doi:10.1128/JVI.02028-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Envelope Determinants of Equine Infectious Anemia Virus Vaccine Protection and the Effects of Sequence Variation on Immune Recognition{triangledown}

Tara L. Tagmyer,1,2 Jodi K. Craigo,2 Sheila J. Cook,3 Deborah L. Even,3 Charles J. Issel,3 and Ronald C. Montelaro2*

Molecular Virology and Microbiology Graduate Program, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261,1 Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261,2 Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky 405163

Received 13 September 2007/ Accepted 21 January 2008

A highly effective attenuated equine infectious anemia virus (EIAV) vaccine (EIAVD9) capable of protecting 100% of horses from disease induced by a homologous Env challenge strain (EIAVPV) was recently tested in ponies to determine the level of protection against divergent Env challenge strains (J. K. Craigo, B. S. Zhang, S. Barnes, T. L. Tagmyer, S. J. Cook, C. J. Issel, and R. C. Montelaro, Proc. Natl. Acad. Sci. USA 104:15105-15110, 2007). An inverse correlation between challenge strain Env variation and vaccine protection from disease was observed. Given the striking differences in protective immunity, we hypothesized that analysis of the humoral and cellular immune responses to the Env protein could reveal potential determinants of vaccine protection. Neutralization activity against the homologous Env or challenge strain-specific Env in immune sera from the vaccinated ponies did not correlate with protection from disease. Cellular analysis with Env peptide pools did not reveal an association with vaccine protection from disease. However, when individual vaccine-specific Env peptides were utilized, eight cytotoxic-T-lymphocyte (CTL) peptides were found to associate closely with vaccine protection. One of these peptides also yielded the only lymphoproliferative response associated with protective immunity. The identified peptides spanned both variable and conserved regions of gp90. Amino acid divergence within the principal neutralization domain and the identified peptides profoundly affected immune recognition, as illustrated by the inability to detect cross-reactive neutralizing antibodies and the observation that certain peptide-specific CTL responses were altered. In addition to identifying potential Env determinants of EIAV vaccine efficacy and demonstrating the profound effects of defined Env variation on immune recognition, these data also illustrate the sensitivity offered by individual peptides compared to peptide pools in measuring cellular immune responses in lentiviral vaccine trials.

* Corresponding author. Mailing address: E1240 Biomedical Science Tower, Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261. Phone: (412) 648-8869. Fax: (412) 383-8859. E-mail: rmont{at}pitt.edu

{triangledown} Published ahead of print on 30 January 2008.

Journal of Virology, April 2008, p. 4052-4063, Vol. 82, No. 8
0022-538X/08/$08.00+0     doi:10.1128/JVI.02028-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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