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UPDATED DECK - n an effort to provide some help, we have analyzed the sequence of the current outbreak virus and provided key T cell epitopes that could be used for T cell assays or vaccine design. The slides are provided below, they are marked non-confidential, and the information is available for use free of any charge of royalty. We only ask that you mention that EpiVax provided the information.
Citation preview
EpiVax Analysis of Ebolavirus:
Zaire Ebolavirus - Mayinga
(the current Ebola outbreak strain)
An immunoinformatics data set for Ebola vaccine
developers
Compiled using EpiVax state-of-the-art tools
For more information see http://bit.ly/EpiVax_Vaccine
• Biotech company based in Providence, Rhode Island
• Owned and operated by Annie De Groot and Bill Martin
Who Are We? (EpiVax)
2
EpiVax designs and develops
safer, more effective biologic
products and vaccines
Engaged
Dedicated to improving human
health everywhere
Cutting Edge
Continuously innovating
thought leaders in
immunoinformatics
Trusted
Highly Published
Trusted by majority of large
Pharma companies
2 8/20/2014 EpiVax - Non-confidential
2014 West Africa Ebola Outbreak Rapidly Expanding Lethal Virus Outbreak
3
http://www.cdc.gov/vhf/ebola/resources/distribution-map-guinea-outbreak.html
8/20/2014 EpiVax - Non-confidential
• Four countries affected: Sierra Leone, Liberia, Guinea, Nigeria
• As of Aug. 15th 2014:
– Suspected and Confirmed Case Count: >2000
– Suspected Case Deaths: >1000
– Mortality Rate: >50%
• No known cure
• No available vaccine
2014 West Africa Outbreak Statistics
4
http://www.cdc.gov/vhf/ebola/outbreaks/guinea/
8/20/2014 EpiVax - Non-confidential
How Can We Help?
• iVAX is a key tool in designing effective vaccines in a rational, efficient manner
• Already providing access to iVAX toolkit to our commercial and academic collaborators
• We can rapidly analyze Ebola for optimal vaccine components
• Perhaps this will be helpful for better design of Ebola vaccines, making it available to the scientific public is what we can do to help.
• Any questions – please contact info@epivax.com
5 8/20/2014 EpiVax - Non-confidential
Why are we releasing findings online:
• EpiVax has unique technology for designing vaccines.
• The technology accurately predicted the high immunogenicity of pandemic H1N1 (only one dose of vaccine needed, most individuals protected by seasonal flu exposure) http://bit.ly/Pandemic_H1N1
• The technology accurately predicted H7N9 low immunogenicity “stealth virus”. http://bit.ly/H7N9_Stealth
• We want to make our contribution to stopping Ebola by making our immunoinformatics analysis of the current virus available world-wide.
EpiVax Contributes to Stopping Ebola
6 8/20/2014 EpiVax - Non-confidential
iVAX – Quick Facts
7
• Comprehensive set of vaccine design tools
• Flexible utilization – vaccine design, antigen engineering, vaccine efficacy analysis
• Applications to assay reagent development and diagnostics (ELISpot assays, e.g.)
• Compatible with modular tool development (ex insertion of tools for animal vaccine design)
• Interactive web access any time
• Involved training program and technical service
8/20/2014 EpiVax - Non-confidential
http://bit.ly/EpiPubs
8
iVAX Toolkit – Commercial
8/20/2014 EpiVax - Non-confidential
iVAX Toolkit – Academic
9
10
Vaccine Design Tools and Techniques
Epitope/Antigen Analysis and Discovery
Vaccine Construct Design/ Optimization
Lab Validation
10
JanusMatrix: Analyze T cell epitope cross-reactivity
TB Epitope
Discovery
Epitope
Validation
Construct
Design
Immuno-
genicity
Tularemia Epitope
Discovery
Epitope
Validation
Construct
Design
Immuno-
genicity
Animal Model
Validation
Smallpox Epitope
Discovery
Epitope
Validation
Construct
Design
Animal Model
Validation
HCV Epitope
Discovery
Epitope
Validation
Construct
Design
Animal Model
Validation
H. pylori Epitope
Discovery
Epitope
Validation
Construct
Design
Animal Model
Validation
Animal Model
Validation
Immuno-
genicity
Immuno-
genicity
Immuno-
genicity
EpiVax Vaccine Design Pipeline
HIV Epitope
Discovery
Epitope
Validation
Construct
Design
Immuno-
genicity
Animal Model
Validation
Influenza Epitope
Discovery
Epitope
Validation
Construct
Design
Immuno-
genicity
Animal Model
Validation
VEEV/EEV Epitope
Discovery
Epitope
Validation
Construct
Design
Immuno-
genicity
Animal Model
Validation
Burkholderia Epitope
Discovery
Epitope
Validation
Construct
Design
Immuno-
genicity
Animal Model
Validation
Selected publications:
12
Publications related to Vaccines 2013-2014
• Lu He, Anne S De Groot, Andres H Gutierrez, William D Martin, Lenny Moise and Chris Bailey-Kellogg.
Integrated assessment of predicted MHC binding and cross-conservation with self reveals patterns of
viral camouflage. BMC Bioinformatics 2014, 15 (Suppl 4): S1 doi:10.1186/1471-2105-15-S4-S1.
http://bit.ly/Viral_Camouflage_2014.
• Zhang S, Desrosiers J, Aponte-Pieras JR, Dasilva K, Fast LD, Terry F, Martin WD, De Groot AS, Moise L,
Moss SF. Human Immune Responses to H. pylori HLA Class II Epitopes Identified by Immunoinformatic
Methods, PLoS One. 2014 Apr 16;9(4):e94974. doi: 10.1371/journal.pone.0094974. eCollection 2014. PMID:
24740005 [PubMed - in process]. http://bit.ly/HPylori_PLOS_One_2014
• De Groot AS, Moise L, Liu R, Gutierrez AH, Terry F, Koita OA, Ross TM, Martin W. Cross-conservation of T-
cell epitopes: now even more relevant to (H7N9) influenza vaccine design. Hum Vaccin Immunother.
2014 Feb;10(2):256-62. doi: 10.4161/hv.28135. Epub 2014 Feb 13. PMID: 24525618 [PubMed - in process].
http://bit.ly/H7N9_Stealth
• Moise L, Gutierrez AH, Bailey-Kellogg C, Terry F, Leng Q, Abdel Hady KM, Verberkmoes N, Sztein MB,
Losikoff P, Martin WD, Rothman A, De Groot AS. The two-faced T cell epitope: Examining the host-
microbe interface with JanusMatrix. Hum Vaccin Immunother. 2013 Apr 12;9(7). PubMed PMID 23584251.
• De Groot AS, Ardito M., Terry, F. Levitz L., Ross T., Moise L., Martin B. Low immunogenicity predicted for
emerging avian-origin H7N9: Implication for influenza vaccine design. Hum Vaccin Immunother. Volume
9, Issue 5 May 2013:950–956 http://dx.doi.org/10.4161/hv.24939 http://bit.ly/H7N9_2013.
http://bit.ly/H7N9_HVandI.
• Moise L, Terry F, Ardito M, Tassone R, Latimer H, Boyle C, Martin WD. Universal H1N1 influenza vaccine
development: Identification of consensus class II hemagglutinin and neuraminidase epitopes derived
from strains circulating between 1980 and 2011. Human Vaccines & Immunotherapeutics 2013; 9:1598 -
1607; PMID: 23846304; http://dx.doi.org/10.4161/hv.25598 8/20/2014 EpiVax - Non-confidential
Selected publications:
13
• Wei R, Xu L, Zhang N, Zhu K, Yang J, Yang C, Deng C, Zhu Z, De Groot AS, Altmeyer R, Zeng M, Leng Q.
Elevated antigen-specific Th2 type response is associated with the poor prognosis of hand, foot and
mouth disease. Virus Res. 2013 Jul 22. doi:pii: S0168-1702(13)00231-1. 10.1016/j.virusres.2013.07.009.
• Leonard Moise, Ryan Tassone, Howard Latimer, Frances Terry, Lauren Levitz, John P. Haran, Ted M. Ross,
Christine Boyle, William D. Martin, Anne S. De Groot. Immunization with Cross-conserved H1N1 Influenza
CD4+ T Cell Epitopes Lowers Viral Burden in HLA DR3 Transgenic Mice. Hum Vaccin Immunother. 2013
Sep 17;9(10). http://bit.ly/H1N1_DR3_2014
• Moise L., Marcello, A, Tassone, R., Cousens, L., Martin, W., De Groot, A.S., Building Better Biotherapeutics
and Vaccines by Design: EpiVax, Inc., an Immunology Company. Rhode Island Medical Journal, February
2013. rimed.org/rimedicaljournal/2013-02/2013-02-19-bio-epivax.pdf
• He Y, Cao Z, De Groot AS, Brusic V, Schönbach C, Petrovsky N. Computational vaccinology and the
ICoVax 2012 workshop. BMC Bioinformatics. 2013;14 Suppl 4:I1.doi: 10.1186/1471-2105-14-S4-I1. Epub
2013 Mar 8. PubMed PMID: 23514034; PubMed Central PMCID: PMC3599086.
• De Groot AS, Einck L., Moise L, Chambers M., Ballantyne J., Malone RW, Ardito M, Martin W. Making
Vaccines “On Demand”: A Potential Solution for Emerging Pathogens and Biodefense? Human
Vaccines and Immunotherapy. Accepted for publication June 27, 2013. http://bit.ly/FastVax
• Leonard Moise, Frances Terry, Andres H. Gutierrez, Ryan Tassone, Phyllis Losikoff, Stephen H. Gregory,
Chris Bailey-Kellogg, William D. Martin, Anne S. De Groot. Time for T? Immunoinformatics addresses the
challenges of vaccine design for NT and EID. Expert Review of Vaccines, Accepted 3 Aug 2014.
• Opinion. Anne S. De Groot, Lenny Moise, Rui Liu, Andres H. Gutierrez, Ryan Tassone, Chris Bailey-Kellogg,
William Martin. Immune Camouflage: Relevance to Vaccine Design and Human Immunology Submitted 3
Aug 2014, July 2014, Human Vaccines and Immunotherapy.
• Moise L, Terry F, Gutierrez AH, Tassone R, Losikoff P, Gregory SH, Martin WD, De Groot AS. Smarter
vaccine design will circumvent regulatory T cell-mediated evasion in chronic HIV and HCV infection. In:
Why vaccines to HIV, HCV and Malaria have so far failed - challenges to developing vaccines against
immunoregulating pathogens. Accepted August 15 2014. Frontiers in Microbiology. 2014. Editor (Gowans).
Steps to Vaccine Design
• Define Pathogen (genome, diagnostic test)
• Correlates of Immunity?
• Critical Antigens - one or many?
• Animal Model? Does it predict protection?
• Prototype Vaccine - Preclinical Proof
• Safety and Toxicity, GMP, Stability
• FDA “IND” (Investigational New Drug)
• Clinical trials (Phase I, II, III)
• FDA Approval / Distribution / Access
14 8/20/2014 EpiVax - Non-confidential
• Circulating strain: Zaire Ebolavirus
Ebolavirus Circulating strain
16 8/20/2014 EpiVax - Non-confidential
Uniprot contains data for 16 Filoviridae strains:
Filoviridae
17
Code Strain EBOEC Zaire ebolavirus (strain Eckron-76) EBOG4 Zaire ebolavirus (strain Gabon-94) EBOIC Ivory Coast ebolavirus (strain Cote d'Ivoire-94)
EBORE Reston ebolavirus (strain Philippines-96)
EBORR Reston ebolavirus (strain Reston-89)
EBORS Reston ebolavirus (strain Siena/Philippine-92) EBOSB Sudan ebolavirus (strain Boniface-76)
EBOSM Sudan ebolavirus (strain Maleo-79) EBOSU Sudan ebolavirus (strain Uganda-00)
EBOZ5 Zaire ebolavirus (strain Kikwit-95)
EBOZM Zaire ebolavirus (strain Mayinga-76) <strain that is analyzed here MABVA Lake Victoria marburgvirus (strain Angola/2005) MABVM Lake Victoria marburgvirus (strain Musoke-80)
MABVO Lake Victoria marburgvirus (strain Ozolin-75) MABVP Lake Victoria marburgvirus (strain Popp-67)
MABVR Lake Victoria marburgvirus (strain Ravn-87)
8/20/2014 EpiVax - Non-confidential
• Data was obtained from Uniprot
• Filoviridae reference dataset was downloaded by searching the Protein Knowledgebase (UniProtKB) (query: taxonomy:11266 AND reviewed:yes)
• 97 retrieved sequences, by protein:
18
iVAX Analysis of Ebola Virus Data Retrieval
Protein Count Protein Count
NP 12 ssGP 5
VP35 10 VP30 10
VP40 11 VP24 11
GP 16 L 11
sGP 11
8/20/2014 EpiVax - Non-confidential
• RNA virus, member of the Filoviridae family (composed of the Cuevavirus, Ebolavirus, and Marburgvirus genera)
• Ebolavirus contains seven genes:
3’ – leader – NP – VP35 – VP40 – GP/sGP – VP30 – VP24 – L – tailer – 5’
• “Envelope glycoprotein” (GP) is the sole protein expressed at the surface of the virus
• GP is likely to be a good candidate for vaccines
Ebolavirus Structure
8/20/2014 EpiVax - Non-confidential 19
“Immunogenicity Scale”
http://bit.ly/EpiPubs
20
The number of T cell epitopes
contained in the sequence of a
protein contributes to its
immunogenicity
Proteins can be compared based on
T cell epitope content per unit
sequence.
20 8/20/2014 EpiVax - Non-confidential
gB-2 (EPX Score: -24.56)
- 80 -
- 70 -
- 60 -
- 50 -
- 40 -
- 30 -
- 20 -
- 10 -
- 00 -
- -10 -
- -20 -
- -30 -
- -40 -
- -50 -
- -60 -
- -70 -
- -80 -
Thrombopoietin
Human EPO
Tetanus Toxin
Influenza-HA
Albumin
IgG FC Region
EBV-BKRF3
Fibrinogen-Alpha
Follitropin-Beta
HA A/California/07/2009 (H1N1)
HA A/Victoria/361/2011 (H3N2)
HA A/Texas/50/2012 (H3N2)
HA A/Anhui/1/2013 (H7N9)
HA A/mallard/Netherlands/09/2005 (H7N7)
Random Expectation
HA A/mallard/Netherlands/12/2000 (H7N3)
HA A/chicken/Italy/13474/1999 (H7N1)
H7 HA Immunogenic Potential
New H7N9 Flu is Predicted to be
POORLY IMMUNOGENIC
http://bit.ly/H7N9_HVandI 8/20/2014 EpiVax - Non-confidential
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis – Immunogenicity Scale
23
• Immunogenicity scale of Zaire Ebolavirus – Mayinga proteins (with EpiMatrix scores) – Red is high potential, blue is low.
Excellent vaccine
candidate
Poor vaccine
candidate
Theoretical minimum
antigenicity score
8/20/2014 EpiVax - Non-confidential
25
ClustiMer tool finds “hot spots”
DRB1*0101
DRB1*0301
DRB1*0401
DRB1*0701
DRB1*0801
DRB1*1101
DRB1*1301
DRB1*1501
• T cell epitopes are not randomly distributed but instead tend to cluster in specific regions. – These clusters can be very powerful, enabling significant immune responses to low-scoring proteins.
• ClustiMer recognizes T cell epitope clusters as polypeptides predicted to bind to an unusually large number of HLA alleles.
• T cell epitope clusters make excellent vaccine candidates:
– compact; relatively easy to deliver as peptides; highly reactive in-vivo 8/20/2014 EpiVax - Non-confidential
26
DNA
Vector
DNA insert
GP protein cartoon with immunogenic epitope clusters in red:
Protein product:
many epitope
clusters as a
“string of beads”
Concept: Multi-Epitope Vaccine Design
GP is the sole protein expressed at the surface of the virus: 676 residues full length
DNA – chain of epitopes, or peptide in liposomes ICS-optimized proteins in VLP ICS-optimized whole proteins
Possible Delivery Platforms
Protein Code # clusters
NP NP_EBOZM 14
VP35 VP35_EBOZM 5
VP40 VP40_EBOZM 7
GP GP_EBOZM 16
sGP SGP_EBOZM 12
ssGP SSGP_EBOZM 10
VP30 VP30_EBOZM 8
VP24 VP24_EBOZM 9
L L_EBOZM 62
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis – Clusters of Promiscuous Epitopes
28
Immunogenic clusters found by ClustiMer in Zaire Ebolavirus – Mayinga
< surface protein
8/20/2014 EpiVax - Non-confidential
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis – Clusters of Promiscuous Epitopes
8/20/2014 29
EpiMatrix scores of GP immunogenic clusters
EpiVax - Non-confidential
iVAX Analysis of Ebola virus Class II HLA Binding Analysis – Clusters of Promiscuous Epitopes
8/20/2014 30
Removed clusters with no EpiBar or high hydrophobicity (highlighted in red, EpiVax standard approach)
EpiVax - Non-confidential
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis – Clusters of Promiscuous Epitopes
8/20/2014 31
• Immunogenicity scale of clusters found in Zaire Ebolavirus – Mayinga GP protein
EpiVax - Non-confidential
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 33
• EpiMatrix maps T cell epitopes across Class II HLA DRB1 alleles
• EpiMatrix report of GP, cluster 16
EpiVax - Non-confidential
Is this cluster conserved in other Ebola strains?
• Homology search of GP, cluster 16
• Conservation among the Filoviridae family (excluding Zaire Ebolavirus – Mayinga), 15 maximum hits
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 34 EpiVax - Non-confidential
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 35 EpiVax - Non-confidential
• EpiMatrix maps T cell epitopes across HLA alleles
• EpiMatrix report of GP, cluster 32
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 36 EpiVax - Non-confidential
Is this cluster conserved in other Ebola strains?
• Homology search of GP, cluster 32
• Conservation among the Filoviridae family (excluding Zaire Ebolavirus – Mayinga), 15 maximum hits
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 37 EpiVax - Non-confidential
• EpiMatrix maps T cell epitopes across HLA alleles
• EpiMatrix report of GP, cluster 85
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 38 EpiVax - Non-confidential
Is this cluster conserved in other Ebola strains?
• Homology search of GP, cluster 85
• Conservation among the Filoviridae family (excluding Zaire Ebolavirus – Mayinga), 15 maximum hits
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 39 EpiVax - Non-confidential
• EpiMatrix maps T cell epitopes across HLA alleles
• EpiMatrix report of GP, cluster 85
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 40 EpiVax - Non-confidential
Is this cluster conserved in other Ebola strains?
• Homology search of GP, cluster 156
• Conservation among the Filoviridae family (excluding Zaire Ebolavirus – Mayinga), 15 maximum hits
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 41 EpiVax - Non-confidential
• EpiMatrix maps T cell epitopes across HLA alleles
• EpiMatrix report of GP, cluster 190
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 42 EpiVax - Non-confidential
Is this cluster conserved in other Ebola strains?
• Homology search of GP, cluster 190
• Conservation among the Filoviridae family (excluding Zaire Ebolavirus – Mayinga), 15 maximum hits
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 43 EpiVax - Non-confidential
• EpiMatrix maps T cell epitopes across HLA alleles
• EpiMatrix report of GP, cluster 215
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 44 EpiVax - Non-confidential
Is this cluster conserved in other Ebola strains?
• Homology search of GP, cluster 215
• Conservation among the Filoviridae family (excluding Zaire Ebolavirus – Mayinga), 15 maximum hits
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 45 EpiVax - Non-confidential
• EpiMatrix maps T cell epitopes across HLA alleles
• EpiMatrix report of GP, cluster 238
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 46 EpiVax - Non-confidential
Is this cluster conserved in other Ebola strains?
• Homology search of GP, cluster 238
• Conservation among the Filoviridae family (excluding Zaire Ebolavirus – Mayinga), 15 maximum hits
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 47 EpiVax - Non-confidential
• EpiMatrix maps T cell epitopes across HLA alleles
• EpiMatrix report of GP, cluster 245
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 48 EpiVax - Non-confidential
Is this cluster conserved in other Ebola strains?
• Homology search of GP, cluster 245
• Conservation among the Filoviridae family (excluding Zaire Ebolavirus – Mayinga), 15 maximum hits
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 49 EpiVax - Non-confidential
• EpiMatrix maps T cell epitopes across HLA alleles
• EpiMatrix report of GP, cluster 336
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 50 EpiVax - Non-confidential
Is this cluster conserved in other Ebola strains?
• Homology search of GP, cluster 336
• Conservation among the Filoviridae family (excluding Zaire Ebolavirus – Mayinga), 15 maximum hits
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 51 EpiVax - Non-confidential
• EpiMatrix maps T cell epitopes across HLA alleles
• EpiMatrix report of GP, cluster 555
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 52 EpiVax - Non-confidential
Is this cluster conserved in other Ebola strains?
• Homology search of GP, cluster 555
• Conservation among the Filoviridae family (excluding Zaire Ebolavirus – Mayinga), 15 maximum hits
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 53 EpiVax - Non-confidential
• EpiMatrix maps T cell epitopes across HLA alleles
• EpiMatrix report of GP, cluster 566
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 54 EpiVax - Non-confidential
Is this cluster conserved in other Ebola strains?
• Homology search of GP, cluster 566
• Conservation among the Filoviridae family (excluding Zaire Ebolavirus – Mayinga), 15 maximum hits
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 55 EpiVax - Non-confidential
• EpiMatrix maps T cell epitopes across HLA alleles
• EpiMatrix report of GP, cluster 579
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis
8/20/2014 56 EpiVax - Non-confidential
Is this cluster conserved in other Ebola strains?
• Homology search of GP, cluster 579
• Conservation among the Filoviridae family (excluding Zaire Ebolavirus – Mayinga), 15 maximum hits
Cluster EPX score
# epitopes TCR-facing residues conservation (1)
Human cross-reactivity (2)
Microbiome cross-reactivity (3)
GP_EBOZM:16 47.6 3 20 % 0 - 4 15 – 43
GP_EBOZM:32 18.95 1 20 % 5 17
GP_EBOZM:85 15.38 1 47 % 0 9
GP_EBOZM:156 17.43 2 60 - 67 % 0 - 2 10 – 19
GP_EBOZM:190 11.22 1 20 % 0 25
GP_EBOZM:215 10.05 1 20 % 1 12
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis – Conservation with Human
8/20/2014 57
The table displays ranges in the case a cluster contains several epitopes.
(1) % of Filoviridae strains with similar TCR-facing residues to the ones in Zaire Ebolavirus – Mayinga epitopes
(2) Number of human sequences with similar TCR-facing residues to the ones in Zaire Ebolavirus – Mayinga epitopes
(3) Number of human microbiome sequences with similar TCR-facing residues to the ones in Zaire Ebolavirus –
Mayinga epitopes
Cross-reactivity analysis of GP clusters (JanusMatrix analysis)
EpiVax - Non-confidential
Cluster EPX score
# epitopes TCR-facing residues conservation (1)
Human cross-reactivity (2)
Microbiome cross-reactivity (3)
GP_EBOZM:238 13.8 1 27 % 2 6
GP_EBOZM:245 28.17 2 13 - 20 % 0 - 16 12 – 139
GP_EBOZM:336 15.84 1 20 % 2 12
GP_EBOZM:555 10.5 1 67 % 0 31
GP_EBOZM:566 22.55 2 67 % 3 - 8 76 – 49
GP_EBOZM:579 20.25 1 27 % 2 21
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis – Conservation with Human
8/20/2014 58
The table displays ranges in the case a cluster contains several epitopes.
(1) % of Filoviridae strains with similar TCR-facing residues to the ones in Zaire Ebolavirus – Mayinga epitopes
(2) Number of human sequences with similar TCR-facing residues to the ones in Zaire Ebolavirus – Mayinga epitopes
(3) Number of human microbiome sequences with similar TCR-facing residues to the ones in Zaire Ebolavirus –
Mayinga epitopes
Cross-reactivity analysis of GP clusters (JanusMatrix analysis)
EpiVax - Non-confidential
• Zaire Ebolavirus – Mayinga surface protein, GP, has a low immunogenic potential at the protein level
• iVAX identified 16 clusters of immunogenicity in the GP sequence
• Several clusters present: – High EpiMatrix scores
– High degree of conservation among Filoviruses
– Low degree of cross-reactivity to human and human microbiome sequences
• iVAX can be used to identify potential targets for vaccine development
iVAX Analysis of Ebola Virus Class II HLA Binding Analysis – Summary
8/20/2014 59 EpiVax - Non-confidential
Class I Immunogenicity screening of Zaire Ebolavirus – Mayinga GP protein
• iVAX identified 143 9-mers and 10-mers sequences with increased immunogenic potential in regards to at least one HLA Class I allele (1)
• From these, 80 sequences present limited homology to human sequences (less than 5 hits)
• From these, 59 sequences have at least one positive hit and no negative hit in IEDB
Please contact bwinterroth@epivax.com for more information.
iVAX Analysis of Ebola Virus Class I HLA Binding Analysis (for details email info@epivax.com)
8/20/2014 65 EpiVax - Non-confidential
(1) HLA-A*0101, HLA-A*0201, HLA-A*0301, HLA-A*2402, HLA-B*0702, HLA-B*4403
• Immunogenicity screening of Zaire Ebolavirus – Mayinga GP protein
iVAX Analysis of Ebola Virus Class I HLA Binding Analysis (for details email info@epivax.com)
8/20/2014 66
143 9-mers and 10-mers with increased immunogenic potential to at least one HLA Class I allele (1)
80 sequences with limited homology to human sequences (less than five hits)
59 sequences with at least one positive hit and no negative hit in IEDB
(1) HLA-A*0101, HLA-A*0201, HLA-A*0301, HLA-A*2402, HLA-B*0702, HLA-B*4403
EpiVax - Non-confidential
• iVAX can:
– Rapidly analyze pathogens
– Evaluate immunogenic potential of peptides against HLA Class I and II alleles
– Quickly identify regions of interest for vaccine development
– Screen candidates against human germline sequences
• We hope our analysis and predictions will help researchers around the world in the fight against Ebola
• Any questions – please contact info@epivax.com
Summary
8/20/2014 68 EpiVax - Non-confidential
Vaccine Collaborations
Don Drake
Brian Schanen
Sharon Frey
Mark Buller
Jill Schreiwer
Hardy Kornfeld
Jinhee Lee
Liisa Selin Connie Schmaljohn
Lesley C. Dupuy
Ted Ross
Mark Poznansky
Tim Brauns
Pierre LeBlanc
AI058326
,
AI058376
,
AI078800
,
AI082642 http://bit.ly/EpiPubs 70
Vish Mokashi
Biswajit Biswas
Manon Cox
Indresh Srivastava
Manabu Ato
Yoshi Takahashi
Drew Hannaman
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