IL-12 Gene as a DNA Vaccine Adjuvant in a Herpes Mouse Model: IL-12 Enhances Th1-Type CD4+ T Cell-Mediated Protective Immunity Against Herpes Simplex Virus-2 Challenge

IL-12 Gene as a DNA Vaccine Adjuvant in a Herpes Mouse Model: IL-12 Enhances Th1-Type CD4+ T Cell-Mediated Protective Immunity Against Herpes Simplex Virus-2 Challenge

IL-12 has been shown to enhance cellular immunity in vitro and in vivo. Recent reports have suggested that combining DNA vaccine approach with immune stimulatory molecules delivered as genes may significantly enhance Ag-specific immune responses in vivo. In particular, IL-12 molecules could constitu...

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Published in:The Journal of immunology (1950) Vol. 162; no. 5; pp. 2912 - 2921
Main Authors: Sin, Jeong-Im, Kim, Jong J, Arnold, Renee L, Shroff, Khushroo E, McCallus, Don, Pachuk, Cathy, McElhiney, Sue P, Wolf, Mary W, Pompa-de Bruin, Sylvia J, Higgins, Terry J, Ciccarelli, Richard B, Weiner, David B
Format: Journal Article
Language:English
Published: United States Am Assoc Immnol 01-03-1999
Subjects:
AIDS/HIV
Animals
Antibodies, Viral - blood
Antigens, Ly - analysis
Chemokine CCL5 - biosynthesis
Cytokines - biosynthesis
Female
Herpesvirus 2, Human - immunology
Interleukin-12 - genetics
Lymphocyte Activation
Mice
Mice, Inbred BALB C
Th1 Cells - immunology
Vaccines, DNA - immunology
Viral Envelope Proteins - genetics
Viral Vaccines - immunology
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Summary:IL-12 has been shown to enhance cellular immunity in vitro and in vivo. Recent reports have suggested that combining DNA vaccine approach with immune stimulatory molecules delivered as genes may significantly enhance Ag-specific immune responses in vivo. In particular, IL-12 molecules could constitute an important addition to a herpes vaccine by amplifying specific immune responses. Here we investigate the utility of IL-12 cDNA as an adjuvant for a herpes simplex virus-2 (HSV-2) DNA vaccine in a mouse challenge model. Direct i.m. injection of IL-12 cDNA induced activation of resting immune cells in vivo. Furthermore, coinjection with IL-12 cDNA and gD DNA vaccine inhibited both systemic gD-specific Ab and local Ab levels compared with gD plasmid vaccination alone. In contrast, Th cell proliferative responses and secretion of cytokines (IL-2 and IFN-gamma) and chemokines (RANTES and macrophage inflammatory protein-1alpha) were significantly increased by IL-12 coinjection. However, the production of cytokines (IL-4 and IL-10) and chemokine (MCP-1) was inhibited by IL-12 coinjection. IL-12 coinjection with a gD DNA vaccine showed significantly better protection from lethal HSV-2 challenge compared with gD DNA vaccination alone in both inbred and outbred mice. This enhanced protection appears to be mediated by CD4+ T cells, as determined by in vivo CD4+ T cell deletion. Thus, IL-12 cDNA as a DNA vaccine adjuvant drives Ag-specific Th1 type CD4+ T cell responses that result in reduced HSV-2-derived morbidity as well as mortality.
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ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.162.5.2912