Journal article
Viral load and clinical disease enhancement associated with a lentivirus cytotoxic T lymphocyte vaccine regimen
Vaccine, Vol.27(18), pp.2453-2468
2009
Handle:
https://hdl.handle.net/2376/114731
PMCID: PMC2773546
PMID: 19368787
Abstract
Effective DNA-based vaccines against lentiviruses will likely induce CTL against conserved viral proteins. Equine infectious anemia virus (EIAV) infects horses worldwide, and serves as a useful model for lentiviral immune control. Although attenuated live EIAV vaccines have induced protective immune responses, DNA-based vaccines have not. In particular, DNA-based vaccines have had limited success in inducing CTL responses against intracellular pathogens in the horse. We hypothesized that priming with a codon-optimized plasmid encoding EIAV Gag p15/p26 with co-administration of a plasmid encoding an equine IL-2/IgG fusion protein as a molecular adjuvant, followed by boosting with a vaccinia vector expressing Gag p15/p26, would induce protective Gag-specific CTL responses. Although the regimen induced Gag-specific CTL in four of seven vaccinated horses, CTL were not detected until after the vaccinia boost, and protective effects were not observed in EIAV challenged vaccinates. Unexpectedly, vaccinates had significantly higher viral loads and more severe clinical disease, associated with the presence of vaccine-induced CTL. It was concluded that (1) further optimization of the timing and route of DNA immunization was needed for efficient CTL priming in vivo, (2) co-administration of the IL-2/IgG plasmid did not enhance CTL priming by the Gag p15/p26 plasmid, (3) vaccinia vectors are useful for lentivirus-specific CTL induction in the horse, (4) Gag-specific CTL alone are either insufficient or a more robust Gag-specific CTL response is needed to limit EIAV viremia and clinical disease, and (5) CTL-inducing vaccines lacking envelope immunogens can result in lentiviral disease enhancement. Although the mechanisms for enhancement associated with this vaccine regimen remain to be elucidated, these results have important implications for development of lentivirus T cell vaccines.
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Details
- Title
- Viral load and clinical disease enhancement associated with a lentivirus cytotoxic T lymphocyte vaccine regimen
- Creators
- Robert H Mealey - Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, United StatesSteven R Leib - Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, United StatesMatt H Littke - Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, United StatesBettina Wagner - Department of Population Medicine and Diagnostic Science, Cornell University, Ithaca, NY 14853, United StatesDavid W Horohov - Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546-0099, United StatesTravis C McGuire - Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, United States
- Publication Details
- Vaccine, Vol.27(18), pp.2453-2468
- Academic Unit
- Veterinary Clinical Sciences, Department of
- Publisher
- Elsevier Ltd
- Identifiers
- 99900547857701842
- Language
- English
- Resource Type
- Journal article