SIV DNA vaccine co-administered with IL-12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques

Jean D. Boyer, Tara M. Robinson, Michele A. Kutzler, R. Parkinson, Sandra A. Calarota, Maninder K. Sidhu, Karuppiah Muthumani, Mark Lewis, George Pavlakis, Barbara Felber, David Weiner

Research output: Contribution to journalArticle

Abstract

Current evidence suggests that a strong induced CD8 human immunodeficiency virus type 1 (HIV-1)-specific cell mediated immune response may be an important aspect of an HIV vaccine. The response rates and the magnitude of the CTL responses induced by current DNA vaccines in humans need to be improved and cellular immune responses to DNA vaccines can be enhanced in mice by co-delivering DNA plasmids expressing immune modulators. Two reported to work well in the mouse systems are interleukin (IL)-12 and CD40L. We sought to compare these molecular adjuvants in a primate model system. The cDNA for macaque IL-12 and CD40L were cloned into DNA vectors. Groups of cynomolgus macaques were immunized with 2 mg of plasmid expressing SIVgag alone or in combination with either IL-12 or CD40L. CD40L did not appear to enhance the cellular immune response to SIVgag antigen. However, more robust results were observed in animals co-injected with the IL-12 molecular adjuvant. The IL-12 expanded antigen-specific IFN-γ positive effector cells as well as granzyme B production. The vaccine immune responses contained both a CD8 component as well a CD4 component, The adjuvanted DNA vaccines illustrate that IL-12 enhances a CD8 vaccine immune response, however, different cellular profiles.

Original languageEnglish
Pages (from-to)262-270
Number of pages9
JournalJournal of Medical Primatology
Volume34
Issue number5-6 SPEC. ISS.
DOIs
Publication statusPublished - Oct 2005

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SAIDS Vaccines
DNA Vaccines
Macaca fascicularis
interleukin-12
Macaca
recombinant vaccines
Interleukin-12
Cellular Immunity
cell-mediated immunity
plasmids
CD40 Ligand
Plasmids
vaccines
adjuvants
Vaccines
immune response
antigens
Antigens
Granzymes
AIDS Vaccines

Keywords

  • DNA
  • HIV
  • IL-12
  • SIV
  • Vaccine

ASJC Scopus subject areas

  • Animal Science and Zoology
  • veterinary(all)

Cite this

Boyer, J. D., Robinson, T. M., Kutzler, M. A., Parkinson, R., Calarota, S. A., Sidhu, M. K., ... Weiner, D. (2005). SIV DNA vaccine co-administered with IL-12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques. Journal of Medical Primatology, 34(5-6 SPEC. ISS.), 262-270. https://doi.org/10.1111/j.1600-0684.2005.00124.x

SIV DNA vaccine co-administered with IL-12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques. / Boyer, Jean D.; Robinson, Tara M.; Kutzler, Michele A.; Parkinson, R.; Calarota, Sandra A.; Sidhu, Maninder K.; Muthumani, Karuppiah; Lewis, Mark; Pavlakis, George; Felber, Barbara; Weiner, David.

In: Journal of Medical Primatology, Vol. 34, No. 5-6 SPEC. ISS., 10.2005, p. 262-270.

Research output: Contribution to journalArticle

Boyer, JD, Robinson, TM, Kutzler, MA, Parkinson, R, Calarota, SA, Sidhu, MK, Muthumani, K, Lewis, M, Pavlakis, G, Felber, B & Weiner, D 2005, 'SIV DNA vaccine co-administered with IL-12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques', Journal of Medical Primatology, vol. 34, no. 5-6 SPEC. ISS., pp. 262-270. https://doi.org/10.1111/j.1600-0684.2005.00124.x
Boyer, Jean D. ; Robinson, Tara M. ; Kutzler, Michele A. ; Parkinson, R. ; Calarota, Sandra A. ; Sidhu, Maninder K. ; Muthumani, Karuppiah ; Lewis, Mark ; Pavlakis, George ; Felber, Barbara ; Weiner, David. / SIV DNA vaccine co-administered with IL-12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques. In: Journal of Medical Primatology. 2005 ; Vol. 34, No. 5-6 SPEC. ISS. pp. 262-270.
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abstract = "Current evidence suggests that a strong induced CD8 human immunodeficiency virus type 1 (HIV-1)-specific cell mediated immune response may be an important aspect of an HIV vaccine. The response rates and the magnitude of the CTL responses induced by current DNA vaccines in humans need to be improved and cellular immune responses to DNA vaccines can be enhanced in mice by co-delivering DNA plasmids expressing immune modulators. Two reported to work well in the mouse systems are interleukin (IL)-12 and CD40L. We sought to compare these molecular adjuvants in a primate model system. The cDNA for macaque IL-12 and CD40L were cloned into DNA vectors. Groups of cynomolgus macaques were immunized with 2 mg of plasmid expressing SIVgag alone or in combination with either IL-12 or CD40L. CD40L did not appear to enhance the cellular immune response to SIVgag antigen. However, more robust results were observed in animals co-injected with the IL-12 molecular adjuvant. The IL-12 expanded antigen-specific IFN-γ positive effector cells as well as granzyme B production. The vaccine immune responses contained both a CD8 component as well a CD4 component, The adjuvanted DNA vaccines illustrate that IL-12 enhances a CD8 vaccine immune response, however, different cellular profiles.",
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