Viral load and clinical disease enhancement associated with a lentivirus cytotoxic T lymphocyte vaccine regimen

Robert H. Mealey, Steven R. Leib, Matt H. Littke, Bettina Wagner, David W. Horohov, Travis C. McGuire

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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.

Original languageEnglish
Pages (from-to)2453-2468
Number of pages16
Issue number18
StatePublished - Apr 21 2009

Bibliographical note

Funding Information:
The important technical assistance of Emma Karel and Lori Fuller is acknowledged. This work was supported in part by U.S. Public Health Service, National Institutes of Health grants AI073101, AI067125, and AI60395.


  • CTL vaccine
  • EIAV
  • Gag DNA prime-vaccinia vector boost
  • IL-2/IgG fusion
  • Lentivirus enhancement
  • Regulatory T cells

ASJC Scopus subject areas

  • Molecular Medicine
  • General Immunology and Microbiology
  • General Veterinary
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases


Dive into the research topics of 'Viral load and clinical disease enhancement associated with a lentivirus cytotoxic T lymphocyte vaccine regimen'. Together they form a unique fingerprint.

Cite this