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Hum Vaccin Immunother. 2012 Nov 1;8(11):1620-9. doi: 10.4161/hv.21407. Epub 2012 Aug 16.

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

Author information

1
Human Retrovirus Pathogenesis Section; Frederick National Laboratory for Cancer Research, Frederick, MD, USA.

Abstract

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.

KEYWORDS:

HIV; SIVmac239; SIVsmE660; antibody; avidity; central memory; effector memory; in vivo electroporation; neutralizing antibody; transitional memory

PMID:
22894956
PMCID:
PMC3601136
DOI:
10.4161/hv.21407
[Indexed for MEDLINE]
Free PMC Article

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