PMID- 10072541
OWN - NLM
STAT- MEDLINE
DCOM- 19990414
LR  - 20071115
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 162
IP  - 5
DP  - 1999 Mar 1
TI  - 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.
PG  - 2912-21
AB  - 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.
FAU - Sin, J I
AU  - Sin JI
AD  - Department of Pathology and Laboratory Medicine, University of Pennsylvania 
      School of Medicine, Philadelphia, PA 19104, USA.
FAU - Kim, J J
AU  - Kim JJ
FAU - Arnold, R L
AU  - Arnold RL
FAU - Shroff, K E
AU  - Shroff KE
FAU - McCallus, D
AU  - McCallus D
FAU - Pachuk, C
AU  - Pachuk C
FAU - McElhiney, S P
AU  - McElhiney SP
FAU - Wolf, M W
AU  - Wolf MW
FAU - Pompa-de Bruin, S J
AU  - Pompa-de Bruin SJ
FAU - Higgins, T J
AU  - Higgins TJ
FAU - Ciccarelli, R B
AU  - Ciccarelli RB
FAU - Weiner, D B
AU  - Weiner DB
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antibodies, Viral)
RN  - 0 (Antigens, Ly)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Cytokines)
RN  - 0 (Vaccines, DNA)
RN  - 0 (Viral Envelope Proteins)
RN  - 0 (Viral Vaccines)
RN  - 0 (glycoprotein D-herpes simplex virus type 2)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Animals
MH  - Antibodies, Viral/blood
MH  - Antigens, Ly/analysis
MH  - Chemokine CCL5/biosynthesis
MH  - Cytokines/biosynthesis
MH  - Female
MH  - Herpesvirus 2, Human/*immunology
MH  - Interleukin-12/*genetics
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Th1 Cells/*immunology
MH  - Vaccines, DNA/*immunology
MH  - Viral Envelope Proteins/*genetics
MH  - Viral Vaccines/*immunology
EDAT- 1999/03/11 00:00
MHDA- 1999/03/11 00:01
CRDT- 1999/03/11 00:00
PHST- 1999/03/11 00:00 [pubmed]
PHST- 1999/03/11 00:01 [medline]
PHST- 1999/03/11 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1999 Mar 1;162(5):2912-21.