An optimized SIV DNA vaccine can serve as a boost for Ad5 and provide partial protection from a high-dose SIVmac251 challenge

Natalie A. Hutnick, Devin J F Myles, Lauren Hirao, Veronica L. Scott, Bernadette Ferraro, Amir S. Khan, Mark G. Lewis, Chris J Miller, Andrew J. Bett, Danilo Casimiro, Niranjan Y. Sardesai, J. Joseph Kim, John Shiver, David B. Weiner

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

One limitation in the development of an improved cellular response needed for an effective HIV-vaccine is the inability to induce robust effector T-cells capable of suppressing a heterologous challenge. To improve cellular immune responses, we examined the ability of an optimized DNA vaccine to boost the cellular immune responses induced by a highly immunogenic Ad5 prime. Five Chinese rhesus macaques received pVax encoding consensus (con) gag/pol/env intramuscularly (IM) with electroporation followed by the Merck Ad5 gag/pol/nef vaccine. A second group of five animals were vaccinated with Merck Ad5 gag/pol/nef followed by pVax gag/pol/env. One year following vaccination, Ad5-prime DNA-boosted monkeys and four unvaccinated controls received an intrarectal challenge with 1000 ID50 SIV mac251. The quality and magnitude of the T-cell response was analyzed by ELISpot and polyfunctional flow cytometry. We observed that an Ad5-prime DNA-boost resulted in significantly elevated SIV-specific T-cell responses even compared with animals receiving a DNA-prime Ad5-boost. Ad5 prime DNA boosted animals were capable of suppressing a pathogenic SIV mac251 challenge. Peak control correlated with the expansion of HLA-DR + CD8 + T-cells two weeks post-infection. These data illustrate that high optimization of a DNA vaccine can drive of immune responses primed by a robust vector system. This previously unachievable feature of these newly optimized DNAs warrants future studies of this strategy that may circumvent issues of serology associated with viral vector prime-boost systems.

Original languageEnglish (US)
Pages (from-to)3202-3208
Number of pages7
JournalVaccine
Volume30
Issue number21
DOIs
StatePublished - May 2 2012

Keywords

  • Adenovirus 5 vaccine
  • DNA vaccine
  • SIV

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

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    Hutnick, N. A., Myles, D. J. F., Hirao, L., Scott, V. L., Ferraro, B., Khan, A. S., Lewis, M. G., Miller, C. J., Bett, A. J., Casimiro, D., Sardesai, N. Y., Kim, J. J., Shiver, J., & Weiner, D. B. (2012). An optimized SIV DNA vaccine can serve as a boost for Ad5 and provide partial protection from a high-dose SIVmac251 challenge. Vaccine, 30(21), 3202-3208. https://doi.org/10.1016/j.vaccine.2012.02.069