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Autoimmune diabetes DNA vaccine pCMV–1/rGAD65 encoding GAD |
Autoimmune diabetes DNA vaccine pND2-GAD65-BAX encoding GAD and BAX |
Autoimmune diabetes DNA vaccine pND2-SGAD55 |
Insulin-dependent diabetes mellitus DNA vaccine JwGAD65 + IL-4 |
| Vaccine Information |
Vaccine Information |
Vaccine Information |
Vaccine Information |
- Vaccine Ontology ID: VO_0004404
- Type: DNA vaccine
- Status: Research
- Host Species as Laboratory Animal Model: Mouse
- gad65
gene engineering:
- Type: DNA vaccine construction
- Description: Vector pCMV expressed glutamic acid decarboxylase (GAD), an initial target islet antigen of autoimmune T cell repertoire (Balasa et al., 2001).
- Detailed Gene Information: Click Here.
- Vector: pCMV-1 (Balasa et al., 2001)
- Immunization Route: Intramuscular injection (i.m.)
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- Vaccine Ontology ID: VO_0004405
- Type: DNA vaccine
- Status: Research
- Host Species as Laboratory Animal Model: Mouse
- BAX
gene engineering:
- Type: DNA vaccine construction
- Description: Vector pND2 expressed secreted BAX (Li et al., 2004).
- Detailed Gene Information: Click Here.
- GAD65
gene engineering:
- Type: DNA vaccine construction
- Description: Vector pND2 expressed secreted GAD (Li et al., 2004).
- Detailed Gene Information: Click Here.
- Vector: pND2 (Li et al., 2004)
- Immunization Route: Intramuscular injection (i.m.)
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- Vaccine Ontology ID: VO_0004403
- Type: DNA vaccine
- Status: Research
- Host Species as Laboratory Animal Model: Mouse
- GAD65
gene engineering:
- Type: DNA vaccine construction
- Description: Vector pND2 expressed sgad55, a modified gad65 cDNA encoding a secreted truncated form of human GAD65 (Filippova et al., 2001).
- Detailed Gene Information: Click Here.
- Vector: pND 2 (Filippova et al., 2001)
- Immunization Route: Intramuscular injection (i.m.)
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- Vaccine Ontology ID: VO_0004406
- Type: DNA vaccine
- Status: Research
- Host Species as Laboratory Animal Model: Mouse
- Antigen: a fusion protein consisting of a portion of murine GAD65 and IgGFc (Tisch et al., 2001)
- Gad65
gene engineering:
- Type: DNA vaccine construction
- Description: Vector Jw4303 expressed a secreted fusion protein consisting of a fragment of glutamic acid decarboxylase 65 (GAD65) linked to IgGFc (Tisch et al., 2001).
- Detailed Gene Information: Click Here.
- IgG Fc
gene engineering:
- Type: DNA vaccine construction
- Detailed Gene Information: Click Here.
- Vector: Jw4303 (Tisch et al., 2001)
- Immunization Route: Intramuscular injection (i.m.)
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| Host Response |
Host Response |
Host Response |
Host Response |
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Mouse Response
- Vaccine Immune Response Type: VO_0003057
- Efficacy: During the 25- week period of monitoring, the GAD65-plasmid DNA vaccination effectively prevented IDDM in young female NOD mice (1/13; 8% incidence). We also immunized mice with GM-CSF encoding GAD65 bicistronic vector (since it is known to recruit antigen-presenting cells, inducing a stronger immune response). However, GAD65–GM-CSF-plasmid DNA immunization (1/8; 12.5% incidence) did not alter the incidence of diabetes (P = 0.6477 vs GAD65-plasmid DNA). Female NOD mice in the control group readily became diabetic beginning at 17 weeks of age (3/12; 25% incidence) and reached a 75% incidence (9/12) at 23 weeks of age (P = 0.001 vs GAD65-plasmid DNA; P = 0.006 vs GAD65– GM-CSF-plasmid DNA) (Balasa et al., 2001).
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Mouse Response
- Vaccine Immune Response Type: VO_0003057
- Efficacy: Data revealed that the only mice showing a significant decrease in diabetes onset were those receiving plasmid pND2-SGAD55-BAX (47% diabetic) compared to mice receiving plasmid pND2-GAD65 (93% diabetic), pND2-GAD65-BAX (87% diabetic), and untreated mice (93% diabetic). Insulitis scoring showed that the decrease in diabetes incidence observed with mice receiving plasmid pND2-SGAD55-BAX was associated with a significant decrease in islet inflammation when compared to untreated mice, and mice receiving either plasmid pND2, pND2-SRUC3, -GAD65-BAX, or -GAD65 (Li et al., 2004).
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Mouse Response
- Vaccine Immune Response Type: VO_0003057
- Efficacy: A Kaplan- Meier plot of diabetes onset, together with statistical analysis, indicated that mice that received injection of pND2- SGAD55 plasmid DNA had a significant reduction in diabetes compared with untreated control animals (P = 0.05; log-rank test). In contrast, mice that received pND2-GAD65 did not show significant diabetes reduction compared with the same controls (P = 0.37; log-rank test) (Filippova et al., 2001).
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Mouse Response
- Vaccine Immune Response Type: VO_0003057
- Efficacy: After monitoring animals up to 58 wk of age, the majority of unimmunized nonobese diabetic (NOD) mice (70%) or animals immunized with JwHEL + IL-4 (75%) or JwGAD65 (83%) had developed diabetes. In contrast, only 17% of NOD mice immunized with JwGAD65 + IL-4 developed diabetes (p = 0.03 vs unimmunized, p = 0.01 vs JwHEL + IL-4, χ2 test) (Tisch et al., 2001).
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| References |
References |
References |
References |
Balasa et al., 2001: Balasa B, Boehm BO, Fortnagel A, Karges W, Van Gunst K, Jung N, Camacho SA, Webb SR, Sarvetnick N. Vaccination with glutamic acid decarboxylase plasmid DNA protects mice from spontaneous autoimmune diabetes and B7/CD28 costimulation circumvents that protection. Clinical immunology (Orlando, Fla.). 2001; 99(2); 241-252. [PubMed: 11318596].
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Li et al., 2004: Li AF, Hough J, Henderson D, Escher A. Co-delivery of pro-apoptotic BAX with a DNA vaccine recruits dendritic cells and promotes efficacy of autoimmune diabetes prevention in mice. Vaccine. 2004; 22(13-14); 1751-1763. [PubMed: 15068859].
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Filippova et al., 2001: Filippova M, Liu J, Escher A. Effects of plasmid DNA injection on cyclophosphamide-accelerated diabetes in NOD mice. DNA and cell biology. 2001; 20(3); 175-181. [PubMed: 11313020].
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Tisch et al., 2001: Tisch R, Wang B, Weaver DJ, Liu B, Bui T, Arthos J, Serreze DV. Antigen-specific mediated suppression of beta cell autoimmunity by plasmid DNA vaccination. Journal of immunology (Baltimore, Md. : 1950). 2001; 166(3); 2122-2132. [PubMed: 11160264].
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