Table 2.

Myelin protein/peptide-based vaccination.

Vaccine	Antigen	Targeting Ligand/Drug	Vaccination Type	Admin. Route	Admin. Dose	Animal Model	Vaccination Outcome
Myelin Proteins/Peptides
MBP [112]	Guinea pig MBP	-	Prophylactic: seven days b.i.	e.c.		SJLxB10.PL female mice (6–8 weeks old) with EAE induced with MBP	Protection from RR form of EAE Reduction of disease incidence to 58%
MBP [113]	Guinea pig MBP	-	Prophylactic: seven and three days b.i. Therapeutic: at initial signs of EAE and after four days	e.c.		B10.PL female mice (6–8 weeks old) with EAE induced with MBP	Prophylactic vaccine: protection from EAE Therapeutic vaccine: suppression of EAE
MBP [114]	Guinea pig MBP	-	Prophylactic: seven and three days b.i.	e.c.		B10.PL and SJLxB10.PL female mice (6–8 weeks old) with acute or RR EAE respectively, induced with MBP Knock out mice: TCRδ_/_, CD1d_/_ and β2m_/_ on H-2u background.	Vaccination with MBP prior to EAE induction prevented the development of the disease (incidence reduction by 50%) and reduced the severity of the clinical symptoms in the mice that developed EAE. Experiments with knock out mice showed that the disease could not be completely suppressed only in β2m_/_ mice.
MOG35–55 [115]	MOG35–55	-	Preclinical/Therapeutic: 3, 5, and 7 days p.i.	i.v.		C57BL/6 female mice (8–10 weeks old) with EAE induced with MOG35–55	Dramatic suppression of EAE development
c-MOG35–55 [116]	MOG35–55 and cyclic- MOG35–55	-	Preclinical/Therapeutic on the same day with immunization and seven days p.i.	s.c.		C57BL/6 female mice (6–10 weeks old) with EAE induced with MOG35–55	Amelioration of EAE clinical course and pathology. Reduction of clinical severity of acute phase of EAE and reduction of overall EAE burden.
ATX-MS-1467 [117]	Mixture of MBP30–44, MBP 131–145, MBP140–154, MBP83–99	-	Prophylactic Preclinical/Therapeutic	s.c.	100 μL of ATX-MS-1467 twice a week	(ObxDR2)F1 mice with EAE induced with spinal cord homogenate	ATX-MS-1467 was shown to effectively prevent and treat EAE. The inhibition of the disease was found to be dose-dependent.
Pool of MBP peptides [118]	MBP68–86 and MBP87–99		Therapeutic: secen and 11 days p.i.	i.n.	500 μg of each MBP peptide /rat	Lewis female rats (9 weeks old) with EAE induced with MBP68–86	Tolerization to a pool of MBP peptides was found to result in amelioration of clinical symptoms of EAE.
MOG35–55 [119]	MOG35–55	-	Prophylactic: every other day, for 10 days b.i.	oral	200 μg of MOG35–55	C57BL/6 male mice (6–8 weeks old) with EAE induced with MOG35–55.	Oral vaccination with MOG35–55 was found capable of efficiently suppressing pathogenic cells.
MBP [120]	MBP	-	Prophylactic: one day b.i.	oral	100 mg of MBP	Euthymic and adult thymectomized Tg mice with EAE induced with MBP.	Euthymic Tg mice were shown to be protected from EAE after oral administration of MBP contrary to thymectomized mice, thus indicating the key role of thymus in oral tolerance induction.
Altered peptide ligands (APLs)
APL [121]	P1: MBP87–99, P2: (Ala91,Ala96)MBP87–99 P3: cyclo(87–99) (Ala91,Ala96)MBP87–99	-	Prophylactic: on the day of immunization	s.c.		Female Lewis rats (6–8 weeks old) with EAE induced with MBP74–85	Suppression of EAE was detected 8 days post P2 and P3 administration. P1 was not found to suppress EAE. P2 was shown to suppress EAE between 8–16 days whereas P3 suppressed EAE until the end of the experiment (e.g., day 18 or 20).
APL [87]	[Ala41]MOG35–55, [Ala41,46]MOG35–55 and [TyrOMe40]MOG35–55 cyclo(46–55)MOG35–55 and cyclo(41–55)MOG35–55	-	Prophylactic: on the day of immunization.	s.c.		C57BL/6 female mice (12–18 weeks old) with EAE induced with rat MOG35–55	Significant reduction of EAE incidence and symptons with the administration of [Ala41,46]MOG35–55 or [Ala41]MOG35–55 as compared with the delivery of [TyrOMe40]MOG35–55, cyclo(46–55)MOG35–55 and cyclo(41–55)MOG35–55
Y-MSPc
Y-MSPc [94]	MOG34–56 MBP89–104 OSP55–80 OSP179–201 MOBP15–36 PLP139–151 PLP178–191	-	Preclinical/Therapeutic: 3, 5, 7, and 21 days p.i.	i.v.	75 μg of Y-MSPc/mouse	SJL/J female mice (2–3 months old) with EAE induced with PLP139–151	Y-MSPc was revealed to be more efficient in inhibiting the development of the disease and suppressing its progression in comparison with a single encephalitogenic peptide or a cocktail of peptides.
Y-MSPc [93]	OSP55–74 MOBP55–77 MOBP15–36 MOG34–56 PLP175–194 PLP139–151 MBP89–104		Preclinical/Therapeutic: administration post immunization	i.v.	75 μg of Y-MSPc/mouse	(C57Bl/6J6SJL/J)F1 mice with EAE induced with PLP139–151 or rhMOG (active classical EAE), or a mixture of hMOG 34–56, hPLP 139–151, hMOBP15–36, hMBP89–104, hOSP55–80 (active complex EAE), or via transfer of line T cells specific for phMOG34–56 or phPLP139–151 (passive EAE)	Y-MSPc was shown to be more efficient in inhibiting the development of classical or complex EAE, suppressing the disease course and reversing the chronic disease, compared with a single encephalitogenic peptide or a cocktail of peptides. Additionally, Y-MSPc appeared to be more effective in suppressing passive EAE.
Cytokine-neuroantigen (NAg) fusion proteins
GMCSF-NAg and MCSF-NAg [60]	Guinea pig MBP69–87	GM-CSF M-CSF cytokines	Therapeutic: Exp.1: 9, 10, 12, and 14 days p.i.; exp. 2: 10, 11, and 13 days p.i.; exp. 3: eight and 11 days p.i.	s.c.	1 nmol of fusion protein(s) per injection (exp. 1 and 2), 4 nmol on day 8 and 1 nmol on day 11 (exp. 3)	Lewis rats with EAE induced with DHFR-NAg fusion protein	GMCSF-NAg was found to potently target MBP69–87 to subsets of myeloid APCs and to successfully induce antigen-specific tolerance.
GMCSF-NAg MCSF-NAg [98]	MBP69–87	GMC-SF MCSF	Prophylactic: 21, 1,4 and 7 days b.i. Therapeutic: 9, 10, 12 and 14 days p.i. (exp. 1), or 10, 11, and 13 days p.i. (exp. 2), or eight and 11 days p.i. (exp. 3)	s.c.	Prophylactic: 4 nmol of fusion protein(s) per injection Therapeutic: 1 nmol (exp. 1 & 2), 4 nmol on day 8 and 1 nmol on day 11 (exp. 3)	Lewis rats with EAE induced with DHFR-NAg fusion protein	Prophylactic vaccination with GMCSF-NAg resulted in attenuation of EAE severity. Furthermore, treatment with GMCSF-NAg successfully inhibited EAE progression to more severe stages.
GMCSF-NAg [122]	MOG35–55	GM-CSF	Preclinical/Therapeutic: p.i.	s.c.	2 or 1 nmol of GMCSF-NAg	C57BL/6 mice with EAE induced with MOG 35–55 (active EAE) or with activated MOG-specific Th1 T cells (passive EAE). SJL mice with EAE induced with PLP139–151. B cell deficient, CD4-deficient, IFN-γR1-deficient, and 2D2	GMCSF-NAg was shown to suppress the established disease especially in passive EAE models. It also proved to be an efficient therapy for Cd4−defficient mice and to exhibit tolerogenic activity in B cell deficient mice.
Cytokine-NAg [97]	MOG35–55 PLP139–151	GM-CSF	Prophylactic: 21, 14 and 7 days b.i. Therapeutic: 13, 15, 17, and 20 days p.i.	s.c.	Prophylactic: 2 nmol of cytokine-NAg Therapeutic: 4 nmol on days 9 and 11, and 2 nmol on day 14 p.i.	C57BL/6 with EAE induced with MOG35–55 (active EAE) or with transfer of activated MOG35–55-specific T lymphocytes. In order to provoke another bout of EAE on day 42, mice were challenged with MOG35–55. SJL mice with EAE induced with PLP139–151.	Fusion of GM-CSF with myelin protein epitopes was found to lead to efficient antigen uptake by myeloid APCs resulting in blocking of the development and progression of EAE.
Cytokine-NAg [96]	MBP69–87 MBP73–87 PLP139–151 MOG35–55	GMCSF IFN-β IL16 IL2	Prophylactic: 21, 14, and 7 days b.i. Therapeutic: 13, 15, 17, and 20 days p.i. or alternatively after the onset of paralysis	s.c.		C57BL/6 mice with EAE induced with MOG35–55. SJL mice with RR EAE induced with PLP139–151. Lewis rats with EAE (acute monophasic form) induced with MBP73–87	The developed cytokine-NAg fusion proteins were shown to target APCs and to successfully prevent the induction of EAE when administered prophylactically as well as to suppress on-going EAE.
Cytokine-NAg [123]	Guinea pig MBP	rat IL-2 or IL-4	Prophylactic: 21, 14 and 7 days b.i. Preclinical/Therapeutic: five days p.i. and on every other day through days 9, 11, or 13 p.i.	s.c.	Prophylactic: 0.5-1 nmol per injection	Lewis rats with EAE induced with guinea pig MBP fusion protein	Prophylactic or therapeutic vaccination with IL-2/NAg resulted in attenuation of EAE course, whereas administration of IL4-NAg indicated lack of tolerogenic activity.
GMCSF-NAg [95]	MOG35–55	GM-CSF	C57BL/6 mice: Prophylactic 21, 14, and 7 days b.i. 2D2-FIG mice: Preclinical/Therapeutic: 0, 7, and 14 days, or 7 and 14 days, or 14 days p.i.	C57BL/6 mice: s.c. 2D2-FIG mice: i.v.	C57BL/6 mice: 2 nmol GMCSF-MOG35–55 per injection 2D2-FIG mice: 4 nmol per injection	C57BL/6 mice with EAE induced with MOG 35–55 2D2-FIG mice with a transgenic MOG-specific repertoire of T cells and a GFP reporter of FOXP3 expression	The pretreatment with the GMCSF-MOG fusion protein elicited CD25+ Tregs which were required for the induction of tolerance. Vaccination of 2D2-FIG with GMCSF-MOG elicited circulating FOXP3+ Tregs the number of which was maintained with multiple boosters.
MOG35–55/I-Ab dimer [107]	MOG35–55	I-Ab dimer	Therapeutic: nine days p.i. (treatment duration: four days).	i.p.	12 nM MOG35–55/I-Ab dimer (1 μg/mouse/day)	C57BL/6 female mice (6–8 weeks old) with EAE induced with MOG35–55	The administration of MOG35–55/I-Ab dimer resulted in the reduction of antigen-specific T cells and amelioration of EAE symptoms.
Antibodies coupled with myelin peptides
α-receptor–MOGp mAbs [100]	DNA for MOG29–59 (MOGp)	α-DEC mAbs α-Langerin mAb	Prophylactic: transfer of MOG-specific CD4+ T cells 15 days b.i. and admin. of α-receptor–MOGp mAbs 14 days b.i.	s.c.	3 μg of α-receptor mAbs	C57BL/6 (B6) mice with EAE induced with MOG35–55	Prophylactic vaccination with α-DEC- and a-Langerin–MOGp mAbs led to reduction of disease incidence, onset delay and amelioration of clinical scores.
αDEC205-PLP139–151 mAb [Stern et al., 2010]	PLP139–151	anti-DEC205	Prophylactic: 10 or 15 days b.i.	i.p.	1 μg of fusion mAb	SJL/J female mice (6–10 weeks old) with EAE induced with PLP 139–151	Administration of αDEC205-PLP139–151 mAb was found to alleviate the disease symptoms.
scFv DEC:MOG [102]	MOG	scFv specific for DEC205	Prophylactic: seven and three days b.i. Therapeutic: oje and four days after disease onset, signified by a clinical score equal to 1	i.v.	10 μg of scFvDEC:MOG	C57/Bl6 mice with EAE induced with WSCH	Almost complete prevention of EAE (90% of mice) was observed by administration of scFv DEC:MOG b.i. Moreover, vaccination with scFv DEC:MOG p.i. resulted in significant alleviation of the clinical symptoms in 90% of the mice.
αDCIR2-PLP139–151 fusion mAb [79]	PLP139–151	αDCIR2	Prophylactic: 10 days b.i.	i.p.	1 μg of fusion mAbs	SJL/J female mice (6–10 weeks old) with EAE induced with PLP139–151 (active EAE) or via adoptive transfer of splenocytes from αDCIR2-PLP139–151-treated mice (passive EAE)	Vaccination with αDCIR2+-PLP139–151 fusion mAb was shown to decrease the severity of the disease and to delay its onset. Mice receiving splenocytes from αDCIR2-PLP139–151-treated mice exhibited substantially lower clinical scores in comparison to those receiving cells from αDCIR2 mAb-treated mice.
αCD4/CD8+PLP139–151 [103]	PLP139–151	Anti-CD4, anti-CD8a Ab	Prophylactic: admin. of mAb 21 days b.i. followed by PLP139–151 delivery every other day for 16 days. Therapeutic: Mice treated with αCD4/CD8 Abs on day 11 p.i. were injected with αCD4/CD8+PLP139–151 every other day from day 12–26.	i.p.	100 μg of CD4-/mouse) 100 μg of CD8a-/mouse 25 μg PLP139–151 per injection	SJL female mice (seven weeks old) with EAE induced with PLP139–151	αCD4/CD8+PLP139–151-treated mice exhibited substantially lower EAE scores and reduced rate of relapses in chronic disease
Recombinant T-cell receptor ligands (RTLs)
RTL342M [124]	MOG35–55	HLA-DR2 peptide-binding domains	Therapeutic (s.c. or i.v.): admin. on the day that the clinical score for each mouse was ≥ 2. Daily admin. for mice receiving multiple doses. Prophylactic (s.c.): admin. of 4, 9, or 14 doses within 15 days. EAE was induced 2 days after the admin. of the final dose.	i.v. s.c.	50 μg of RTL342M	HLA-DR2 positive male/female mice (8–12 weeks old) with EAE induced with MOG35–55	RTL treatment was revealed to be more efficient in reducing paralysis when administered in the form of multiple doses instead of a single dose, independently of the administration mode. Furthermore, the treatment with RTL342M could treat or prevent relapses. Pretreatment with RTL342M was shown to prevent the disease.
RTL401 [125]	PLP139–151	α1 and β1 domains of the I-As class II molecule	Upon EAE onset, daily i) i.v. admin. for 3–4 days and ii) s.c. admin. for 8 days.	i.v. s.c.	100 μg of RTL401	SJL mice (6–7 weeks of age) with EAE induced with PLP139–151 or PLP178–191 or MBP84–104. C57BL/6 X SJL) F1 mice (6–7 weeks of age) with EAE induced with MOG35–55 or PLP139–151.	i.v. or s.c. vaccination with RTL401 resulted in prevention of relapses and long-term reduction of clinical severity only in SJL mice and C57BL/6 X SJL) F1 mice with EAE induced with PLP139–151.
RTL401 [126]	PLP139–151	α1 and β1 domains of the I-As class II molecule	Upon EAE onset, daily (i) i.v. admin. for five days and (ii) s.c. for eight days.	i.v. s.c.	100 μL of 1 mg/mL RTL401	SJL female mice (7–8 weeks old) with EAE induced with PLP139–151 (active EAE) or via transfer of activated PLP139–150-specific T cells (passice EAE)	i.v. or s.c. vaccination with RTL401 was shown to effectively discontinue passive EAE progression, reverse its clinical severity and reduce the infiltration of cells into the CNS, as in the treatment of active EAE. Injury to axons was also prevented.
RTL551 [127]	MOG35–55	α1 and β1 domains of the I-Ab class II molecule	Upon EAE onset (days 12–14 for active EAE and days 7–12 for passive EAE), daily i.v. admin. for five days.	i.v.	100 μL of 1 mg/mL RTL551	C57BL/6 male mice (6–7 weeks of age) with EAE induced with MOG35–55 (active EAE) or via transfer of activated cells (passive EAE).	RTL551 treatment of actively or passively induced EAE resulted in significant reduction of clinical symptoms and spinal cord lesions.
RTL401, RTL402, RTL403 [128]	PLP139–151 PLP178–191 MBP84–104	α1 and β1 domains of the I-As class II molecule	At EAE onset (days 10-11), when the clinical score was ≥2, daily s.c. admin. for 8 days.	s.c.	100 μL of 1 mg/mL RTL	SJL/J female mice (7–8 weeks old) with EAE induced with WSCH or with a mixture of PLP139–151 and PLP178–191.	A single RTL was found capable of successfully treating ongoing disease induced with a mixture of encephalitogenic epitopes as long as the cognate T cell specificity was present.
RTL551 [106]	rhMOG, hMOG35–55, mMOG35–55	α1 and β1 domains of the I-Ab class II molecule	At EAE onset (days 10–13), when the clinical score was ≥2, daily i.v. admin. for eight days.	i.v.	100 μL of 1 mg/mL RTL551	C57BL/6 male mice (7–8 weeks old) with EAE induced with rhMOG or mMOG35–55.	Vaccination with RTL551 could reverse the progression of EAE, reduce demyelination and damage of axons without however induce suppression of anti-MOG Ab response.
RTL401 [129]	PLP139–151	α1 and β1 domains of the I-As class II molecule	Upon EAE onset (days 10–11), daily admin. for 1, 2, or 5 days.	s.c.	100 μL of 1 mg/mL RTL401	SJL/J female mice (7–8 weeks old) with EAE induced with PLP139–151 (active EAE) or via transfer of activated cells (passive EAE). TCR Tg 5B6 mice with EAE induced with PLP139–151 B cell deficient (μMT knock-out, KO) mice on C57BL/6 background (7–8 weeks old) with EAE induced with MOG35–55.	A new interaction between cells was revealed via which the RTL-equipped myeloid APCs reverse EAE progression by transferring tolerogenic signals to cognate T lymphocytes. It was also found that splenocytes incubated with RTL401 exhibited reduced ability to passively transfer EAE. Finally, it was shown that EAE can be treated by RTL551 in the absence of B cells.
VG312, VG303, VG311 [108]	MOG35–55, MBP85-99, CABL	α1 and β1 domains of DR2	Therapeutic: i.v. administration for eight consecutive days, 2–4 days after the disease onset.	i.v.	100 μL of VG312, VG303, VG311	Tg HLA-DR2 male and female mice (8–12 weeks old) with EAE induced with MOG35–55	Vaccination with VG312 led to peptide- and dose-dependent induction of long-term tolerance to the encephalitogenic epitope MOG35–55 and reversal of the clinical/histological symptoms of EAE
RTL401 [130]	PLP139–151	α1 and β1 domains of the I-As class II molecule	Therapeutic: (i) i.v. admin. for five consecutive days (days 20–24) and (ii) s.c. admin. for 3 days (days 32–34).	i.v. s.c.	100 μg of RTL401	SJL/J female mice (7–8 weeks old) with EAE induced with PLP139–151.	Administration of RTL401 post the relapsing EAE peak resulted in prevention of disease relapses, reduction of demyelination and axonal damage.
Bifunctional peptide inhibitor (BPI)
PLP-B7AP [131]	PLP139–151	B7 antisense peptide (AP) derived from CD28 receptor	Prophylactic 11, 8, and 5 days b.i. Preclinical/Therapeutic: 4, 7, and 10 days p.i.	s.c.	Prophylactic: 50 or 100 nmol PLP-B7AP/injection Therapeutic: 100 nmol PBI/injection	SJL/J female mice (5–7 weeks old) with EAE induced with PLP139–151	Both prophylactic and therapeutic vaccination with PLP-B7AP resulted in efficient suppression of EAE. Mice treated with PLP-B7AP exhibited significantly low demyelination.
PLP-LABL [132]	PLP139–151	LABL	Prophylactic: 11, 8, and 5 days b.i.	s.c.	100 nmol/injection/day	SJL/J female mice (5–7 weeks old) with EAE induced with PLP	The vaccination with PLP-LABL inhibited the inflammatory response resulting in prevention of BBB disruption and thus inhibition of EAE onset and progression.
PLP-LABL derivatives [110]	PLP139–151	LABL	Therapeutic: admin. on disease onset, signified by a clinical score ≥1, and for three consecutive days until the score was <1)	i.v.	100 nmol/mouse	SJL/J (H-2S) female mice (5–7 weeks old)	Vaccination with the synthesized BPI derivatives was shown to efficiently inhibit EAE severity, and incidence.
PLP-LABL [133]	PLP139–151	LABL	Preclinical/Therapeutic: 4, 7, 10, and 14 days p.i.	i.v.	100 mol/mouse	SJL/J female mice (5–7 weeks old) with EAE induced with PLP139–151	Low disease scores and incidence could be observed in mice vaccinated with PLP-LABL.
PLP-LABL derivatives [134]	PLP139–151	LABL	Therapeutic: admin. on disease onset, signified by a clinical score ≥1, and for three consecutive days until the score was <1)	i.v.	100 nmol/mouse	SJL/J female mice (5–7 weeks old) with EAE induced with PLP139–151	The synthesized BPI derivatives were revealed to suppress EAE progression after intravenous administration more efficiently in comparison with unmodified BPI.
BPI-Fc fusion peptides LABL-Fc-ST-PLP and LABL-Fc-ST-MOG [109]	PLP139–151 MOG38–50	LABL-Fc-ST	Preclinical/Therapeutic: four and seven days p.i.	i.v.	25 nmol per dose	SJL/J mice (5–7 weeks old) with EAE induced with PLP139–151	BPI-Fc fusion peptides were revealed to be highly efficient in suppressing EAE. The vaccinated mice were not found to exhibit weight loss, and featured benign clinical symptoms and reduced demyelination.
PLP–cIBR Derivatives [135]	PLP139–151	cIBR7 peptide	Studies I and II: 4, 7, and 10 days p.i. Study III: admin. on disease onset, signified by a clin. score ≥1, and for 3 consecutive days until the score was <1	i.v.	Study I: 100 nmol/injection/day Study II and III: 50 nmol/injection/day	SJL/J (H-2S) female mice (5–7 weeks old) with EAE induced with PLP139–151	Vaccination with PLP–cIBR, even at low dose or less frequent i.v. injections, resulted in significant amelioration of EAE and protected CNS against demyelination.
Multivalent BPI (MVBMOG/PLP) [111]	MOG38–50 PLP139–151	LABL	Preclinical/Therapeutic 4, 7, and 10 days p.i.	s.c.	100 nmol/mouse	SJL/J female mice (5–7 weeks old) with EAE induced with PLP139–151 C57BL/6 mice (4–6 weeks old) with EAE induced with MOG38–50	MVBMOG/PLP was found to significantly suppress EAE in both animal models despite the evidence of epitope spreading in the C57BL/6 mice.
Antigen-drug conjugates
PLP139−151-DEX [61]	PLP139−151	DEX	Preclinical/Therapeutic: 4, 7, and 10 days p.i.	s.c.		SJL/J female mice (4–6 weeks old) with EAE induced with PLP139–151	Vaccination with PLP139–151-DEX efficiently protected the SJL/J mice from the onset of clinical symptoms compared with DEX treatment.

MBP: myelin basic protein; b.i.: before immunization; EAE: experimental autoimmune encephalomyelitis; e.c.: epicutaneous; RR: relapsing-remitting; MOG: myelin oligodendrocyte glycoprotein; p.i.: post immunization; i.n.: intranasal; APL: altered peptide ligand; Y-MSPc: recombinant synthetic protein comprising multiple epitopes of the human myelin protein; OSP: oligodendrocyte-specific protein; MOBP: myelin associated oligodendrocyte basic protein; PLP: proteolipid protein; GMCSF: Granulocyte-macrophage colony-stimulating factor; MCSF: macrophage colony stimulating factor; DHFR: dihydrofolate reductase; i.p.: intraperitoneal; IFN: interferon; IL: interleukin; mAbs: monoclonal antibodies; scFv: single chain fragment variables; WSCH: whole spinal cord homogenate; RTL: recombinant T-cell receptor ligand; HLA: human leucocyte antigen; rhMOG: recombinant human MOG; mMOG: murine MOG; BPI: bifunctional peptide inhibitor; LABL: ICAm-I binding peptide; DEX: dexamethasone.