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Generation of robust immunity following DNA vaccination enhanced by intradermal electroporation
Trevor Smith, PhD
Cell & Gene Therapy 2014,Las Vegas, NV
October 27–29, 2014
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Vaccines: Safety vs. EfficacyVaccines: Safety vs. Efficacy
IAVI Blueprint for AIDS Vaccine Report, 2008
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Inovio: Fulfilling the promise of DNA VaccinesInovio: Fulfilling the promise of DNA Vaccines
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Enhanced DNA Delivery: in vivo Electroporation
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Electroporation Enhanced TransfectionElectroporation Enhanced Transfection
Sardesai and Weiner, Curr. Opin. Immunol. 2011
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Therapeutic Phase I
HPV-001 InovioHPV-002 Inovio HIV-001 UPenn – PennVax BHPV-004 Inovio (open IND)HPV-005 Inovio (open IND)HPV-006 Inovio (Open IND)
Therapeutic Phase II
HPV-003 Inovio Cervical Dysplasia
VGX-3100 (HPV16/18 E6 & E7 oncoproteins)
Prophylactic Phase I
HIV-080 HVTN – PennVax BFLU-001 Inovio (US)FLU-001 Inovio (Korea)RV-262 Army – PennVax B and G
Number patients treated - 520+ Total immunizations - 1300+
Muscle EP Device – In the clinic: CELLECTRA®-5PMuscle EP Device – In the clinic: CELLECTRA®-5P
Phase III Device
IM-Electroporation
Series10
10
20
30
40
50
60
70
Perc
ent
VGX-3100 Placebo
Phase II efficacy:Lesion regression + viral
clearance
40.2 %
14.3 %
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Surface EP System Intradermal Electroporation
x20 x20
pGFP
1. Mantoux injection to admin. pDNA
GFP
2. EP to allow pDNA transfection
Skin EP Device – preclinical: SEPSkin EP Device – preclinical: SEP
ID injection + SEP procedure:
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Stratum corneum
Epidermis
Dermis
Surface EP specifically targets the Epidermis
Smith TRF et al, Mol. Ther. – Methods & Clinical Dev. In press
K10/RFP/Hoescht
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Advantages of vaccinating in the skinAdvantages of vaccinating in the skin
Immunocompetence:
epid
erm
is
Dendritic cells
Diehl MC et al, Hum Vacc. Imm. 2013
Accessibility
Monitoring
Tolerability:
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Proposed Mechanism
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IMARIS-3D Rendered
RFP positive dendritic cell
Epidermis:
Dermis:
Directly transfecting Dendritic Cells
Amante D et al, Human Gene Therapy. In press
x 60
GFP positive dendritic cell
GFP MsGp2
Color merged
GFP MsGp2
Dendritic cell staining in dermis:
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Kinetics of DC migration into the dermis
Number of GFP+ cellsIn the dermis:
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GFP+ cells in the draining lymph nodes
GFP+ cell in the T cell zone of the cortex in the inguinal lymph node
CD4/GFP/Dapi
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Treatment site excision and host immune responses
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Summary
Surface EP
• Transfection ofepidermal DCs
• Prime ImmuneResponse
• Migration intodermis
• Traffic to the DLN
Vaccine Indications:
Influenza
Ebola
Travel vaccines
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Acknowledgments
Kate BroderickJay McCoy Janess MendozaDinah Amante
Katherine SchultheisAlan GomezLaurent HumeauNiranjan SardesaiJ. Joseph Kim
Bill Kiosses
This work was supported in part by US Army grant W23RYX-8141-N604: #08023003 and US Army SBIR W81XWH-11-C-0051:# 1031550133.
Additional funding support from DTRA and NIH/NIAID
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Inovio combines optimized DNA with safe & effective delivery to generate significant T cells with killing activity
18
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Epidermis
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Series10
10
20
30
40
50
60
70
Perc
ent
VGX-3100 Placebo
Overall Histopathologic Regression* andVirological (HPV Type 16 or 18) Clearance Incidence
Per-Protocol** Population (N=142)
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Inovio: Fulfilling the promise of DNA VaccinesInovio: Fulfilling the promise of DNA Vaccines
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Surface EP System Intradermal Electroporation
+ EP- EP
GFP expression on skin surfacex40
x20 x20
+ EP- EP
GFP expression in epidermis
pGFP
1. Mantoux injection to admin. pDNA
GFP
2. EP to allow pDNA transfection
Skin EP Device – preclinical: SEPSkin EP Device – preclinical: SEP