Enhancement of VP1-specific immune responses and protection against EMCV-K challenge by co-delivery of IL-12 DNA with VP1 DNA vaccine.
It has been reported that co-delivery of IL-12 DNA with a DNA vaccine further enhances antigen (Ag)-specific protective immunity in pathogenic challenge models. However, the enhancing effects of antibody by IL-12 have been controversial. To clarify this issue, we constructed an IL-12 expression vector, co-immunized IL-12 DNA with an encephalomyocarditis virus (EMCV)-D VP1 plasmid vaccine, and then evaluated immune modulatory effects and protection against lethal EMCV-K challenge. We observed that VP1-specific IgG production, as well as seroconversion rates, were significantly enhanced by IL-12 co-injection, indicating that IL-12 can enhance antibody responses in this model system. In particular, co-injection with VP1 plus IL-12 DNA into the same leg enhanced systemic Ag-specific IgG production to a significantly greater extent than either the separate leg injection of VP1 and IL-12 DNA or VP1 DNA vaccine alone. This suggests that local co-expression of IL-12 along with antigens is more important for enhanced antibody production. Furthermore, IgG2a isotype was significantly enhanced by IL-12 DNA co-injection, indicating a Th1 bias. In addition, co-delivery of IL-12 DNA was demonstrated to enhance VP1-specific Th cell proliferative responses. When animals were challenged with a lethal dose of EMCV-K, IL-12 DNA-co-immunized animals exhibited enhanced survival, as compared to VP1 DNA vaccine alone. These studies suggest that IL-12 plays an important role in increasing Ag-specific Th1 type antibody and cellular responses, resulting in enhanced protection against lethal EMCV-K challenge.
Suh
Y S
YS
National Research Lab., Department of Life Science, Pohang University of Science and Technology, San 31, Hyoja-Dong, Pohang, 790-784, Kyungbuk, South Korea.
Ha
S J
SJ
Lee
C H
CH
Sin
J I
JI
Sung
Y C
YC
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000918:Antibody Specificity; D002213:Capsid / Q000276:immunology*; D036022:Capsid Proteins; D018188:Cardiovirus Infections / Q000276:immunology / Q000517:prevention & control; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D004686:Encephalomyocarditis virus / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D005260:Female; D005822:Genetic Vectors; D007074:Immunoglobulin G / Q000096:biosynthesis; D018664:Interleukin-12 / Q000235:genetics*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000235:genetics
D000914:Antibodies, Viral; D036022:Capsid Proteins; D007074:Immunoglobulin G; C096256:VP1 protein, encephalomyocarditis virus; D019444:Vaccines, DNA; D014765:Viral Vaccines; D018664:Interleukin-12; D004247:DNA