IL-12 DNA as molecular vaccine adjuvant increases the cytotoxic T cell responses and breadth of humoral immune responses in SIV DNA vaccinated macaques.

Published

Journal Article

Intramuscular injection of macaques with an IL-12 expression plasmid (0.1 or 0.4 mg DNA/animal) optimized for high level of expression and delivered using in vivo electroporation, resulted in the detection of systemic IL-12 cytokine in the plasma. Peak levels obtained by day 4-5 post injection were paralleled by a rapid increase of IFN-γ, indicating bioactivity of the IL-12 cytokine. Both plasma IL-12 and IFN-γ levels were reduced to basal levels by day 14, indicating a short presence of elevated levels of the bioactive IL-12. The effect of IL-12 as adjuvant together with an SIVmac239 DNA vaccine was further examined comparing two groups of rhesus macaques vaccinated in the presence or absence of IL-12 DNA. The IL-12 DNA-adjuvanted group developed significantly higher SIV-specific cellular immune responses, including IFN-γ (+) Granzyme B (+) T cells, demonstrating increased levels of vaccine-induced T cells with cytotoxic potential, and this difference persisted for 6 mo after the last vaccination. Coinjection of IL-12 DNA led to increases in Gag-specific CD4 (+) and CD4 (+) CD8 (+) double-positive memory T cell subsets, whereas the Env-specific increases were mainly mediated by the CD8 (+) and CD4 (+) CD8 (+) double-positive memory T cell subsets. The IL-12 DNA-adjuvanted vaccine group developed higher binding antibody titers to Gag and mac251 Env, and showed higher and more durable neutralizing antibodies to heterologous SIVsmE660. Therefore, co-delivery of IL-12 DNA with the SIV DNA vaccine enhanced the magnitude and breadth of immune responses in immunized rhesus macaques, and supports the inclusion of IL-12 DNA as vaccine adjuvant.

Full Text

Duke Authors

Cited Authors

  • Jalah, R; Patel, V; Kulkarni, V; Rosati, M; Alicea, C; Ganneru, B; von Gegerfelt, A; Huang, W; Guan, Y; Broderick, KE; Sardesai, NY; LaBranche, C; Montefiori, DC; Pavlakis, GN; Felber, BK

Published Date

  • November 1, 2012

Published In

Volume / Issue

  • 8 / 11

Start / End Page

  • 1620 - 1629

PubMed ID

  • 22894956

Pubmed Central ID

  • 22894956

Electronic International Standard Serial Number (EISSN)

  • 2164-554X

Digital Object Identifier (DOI)

  • 10.4161/hv.21407

Language

  • eng

Conference Location

  • United States