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EAE
IDDM
Immunizing transgenes
• Insulin B chain (plasmid)
• IgFc-GAD65 (plasmid, retrovirus), spGAD65 (plasmid)
• hsp60 (plasmid)
1
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IDDM
Immunodeviation
IgFc-GAD65
IL10
spGAD65
EXPERIMENTAL ARTHRITIS
Immunizing transgenes
• Collagen type II (plasmid)
• C-C chemokines: MCP-1, MIP-1a, MIP-1b, RANTES (plasmid)
• TNFa (plasmid)
2
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EXPERIMENTAL
ARTHRITIS
Neutralizing antibodies
Table 1. Protocols of DNA vaccination applied succesfully to experimental autoimmune diseases
Disease
Antigenic target
EAE
TCR Vb 8.2
MBP
PLP
MOG
IDDM
Insulin
GAD65
Soluble GAD65
Hsp60
Arthritis
Vector
Plasmid and viral
(adenovirus,
vaccinia virus)
Plasmid
Plasmid
Plasmid
Associated molecules
Induced pathway of
immune response
Reference N.
None
IgG-binding ZZ protein
None; IL-4
None
Th1 activating Th2
Th1 activating Th2
Th1 to Th2 immunodeviation
Th1
22,23,24
25
26
27
Plasmid
Plasmid and virus (r)
Plasmid
Plasmid
None (LCMV mice);
IL-4 (NOD mice)
Ig-Fc or IL-4
None; Bax
None
Th1 to Th2
immunodeviation,
induction of Tregs
Th1 to Th2 immunodeviation
Th1 to Th2 immunodeviation,
Treg activation
(CD4+CD25+)
Th1 to Th2 immunodeviation
29,30,32,33
28-34
35
36
Collagen type II
C-C chemokines
TNFa
Plasmid
Plasmid
Plasmid
IL-4
None
None
Th1 to Th2 immunodeviation
Neutralizing antibodies
Neutralizing antibodies
37
39
40
Uveitis
Protein S
Viral vector
(retrovirus)
None
Undetermined
42
SLE
Consensus peptide
(pCons)
Plasmid
None
Induction of T suppressors
(CD8+CD28-)
Antiphospholipid
syndrome
TNFa
Plasmid
None
Neutralizing antibodies
F.Ferrera et al
41
3
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SLE
NUCLEOSOME
4
27/02/2013
5
27/02/2013
IDIOTYPIC NETWORK IN SLE
Anti-dsDNA Abs
Treg
pCons
pCons: a consensus peptide derived from immunogenic sequences from
variable regions of different anti-dsDNA mAbs.
6
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EcoRI
EcoRI
XbaI
pIgCons plasmid
ATG
pCMV
hIgG1 Fc
pNEG
hIgG1 Fc
EcoRI
EcoRI
XbaI
pIgNeg plasmid
pCONS
ATG
pCMV
EcoRI
XbaI
EcoRI
pIg plasmid
ATG
pCMV
hIgG1 Fc
7
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Somatic transgene immunization
B
Fc
pCons
B
8
