Download - EpiVax Analysis of Ebolavirus Zaire Ebolavirus - Mayinga (the current Ebola Outbreak Strain)
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)
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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 EpiVax -‐ Non-‐non-‐confiden1al 2
2014 West Africa Ebola Outbreak Rapidly Expanding Lethal Virus Outbreak
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http://www.cdc.gov/vhf/ebola/resources/distribution-map-guinea-outbreak.html
• 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
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http://www.cdc.gov/vhf/ebola/outbreaks/guinea/
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 [email protected] EpiVax -‐ Non-‐non-‐confiden1al 5
Why are we releasing findings online: • EpiVax has unique technology for designing vaccines. • The techology accurately predicted the high immunogenicity of pandemic H1N1 (only one dose of vaccine needed, most individuals protected by seasonal flu exposure) h^p://bit.ly/Pandemic_H1N1
• The techology accurately predicted H7N9 low immunogenicity “Stealth virus”. h^p://bit.ly/H7N9_Stealth
• We would like to make our contribu1on to stopping Ebola by making our immunoinforma1cs analysis of the current virus available world-‐wide.
EpiVax Contributes to Stopping Ebola
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iVAX – Quick Facts
EpiVax -‐ Non-‐non-‐confiden1al 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 anytime • Involved training program and technical service
h^p://bit.ly/EpiPubs 8
iVAX Toolkit – Commercial
EpiVax -‐ Non-‐non-‐confiden1al
iVAX Toolkit – Academic
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Vaccine Design Tools and Techniques
Epitope/Antigen Analysis and Discovery
Vaccine Construct Design/ Optimization
Lab Validation
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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:
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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
Selected publications:
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Publications related to Vaccines 2013-2014 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 Review. 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 Proceedings. 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. Review. 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 neglected tropical and emerging infectious diseases. 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).
Selected publications:
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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
EpiVax -‐ Non-‐non-‐confiden1al 15
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
EpiVax -‐ Non-‐non-‐confiden1al 16
• 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’
• GP is the sole protein expressed at the surface of the virus
• GP is likely to be a good candidate for vaccines
Ebolavirus Structure
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• Circula1ng strain: Zaire Ebolavirus
Ebolavirus Circulating strain
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• Uniprot contains data for 16 Filoviridae strains:
Filoviridae
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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)
• 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:
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iVax Analysis of Ebola virus Data Retrieval
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Protein Count Protein Count
NP 12 ssGP 5
VP35 10 VP30 10
VP40 11 VP24 11
GP 16 L 11
sGP 11
“Immunogenicity Scale”
h^p://bit.ly/EpiPubs
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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.
EpiVax - Non-non-confidential 21
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 ExpectaOon
HA A/mallard/Netherlands/12/2000 (H7N3)
HA A/chicken/Italy/13474/1999 (H7N1)
H7 HA Immunogenic PotenOal
New H7N9 Flu is Predicted to be POORLY IMMUNOGENIC
http://bit.ly/H7N9_HVandI
iVax Analysis of Ebola virus Class II Analysis
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• Immunogenicity scale of Zaire Ebolavirus – Mayinga proteins (with EpiMatrix scores) – Red is high poten1al, blue is low.
Excellent candidate
Poor candidate
Theore1cal minimum an1genicity
score
PotenOal Ags Ebola Zaire
- 80 -
- 70 -
- 60 -
- 50 -
- 40 -
- 30 -
- 20 -
- 10 -
- 00 -
- -10 -
- -20 -
- -30 -
- -40 -
- -50 -
- -60 -
- -70 -
- -80 -
Albumin
IgG FC Region Fibrinogen-Alpha
Tetanus Toxin
Influenza H3N1-HA
GP_EBOZM (-14.74)
L_EBOZM (34.64)
NP_EBOZM (-12.17)
SGP_EBOZM (6.03) SSGP_EBOZM (11.84)
VP24_EBOZM (95.68)
VP30_EBOZM (5.73)
VP35_EBOZM (-22.18) VP40_EBOZM (-18.01)
Influenza H7N9-HA
EBV-BKRF3
HBV S Ag
EpiVax - Non-non-confidential 25
ClustiMer – 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.
• Clus1Mer recognizes T-‐cell epitope clusters as polypep1des predicted to bind to an unusually large number of HLA alleles.
• T-‐cell epitope clusters make excellent vaccine candidates:
– compact; rela1vely easy to deliver as pep1des; highly reac1ve in-‐vivo
iVax Analysis of Ebola virus Class II Analysis – Clusters promiscuous epitopes
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• Clusters iden1fied for Zaire Ebolavirus – Mayinga proteins
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 Analysis
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• Immunogenic clusters found by Clus1Mer in Zaire Ebolavirus – Mayinga
iVax Analysis of Ebola virus Class II Analysis
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• EpiMatrix scores of GP’s immunogenic clusters
iVax Analysis of Ebola virus Class II Analysis
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• Removed clusters with no EpiBar or high hydrophobicity (EpiVax standard approach)
iVax Analysis of Ebola virus Class II Analysis
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• Immunogenicity scale of clusters found in Zaire Ebolavirus – Mayinga GP protein
Tetanus Toxin (825-850)
HCV NPC NS3 (1248-1267)
Influenza HA (306-319)
Tetanus Toxin (947-967)
Human CLIP
EBV BHRF1(171-189)
20-mer Theoretical Minimum
- +40 -
- -
- +30 -
- -
- +20 -
- -
- +10 -
- -
- 0.0 -
- -
- -10 -
PROTEIN ADDRESS SCORE
GP_EBOZM 16 – 38 47.6
GP_EBOZM 245 – 265 28.17
GP_EBOZM 566 – 583 22.55
GP_EBOZM 579 – 595 20.25
GP_EBOZM 32 – 49 18.95 GP_EBOZM 156 – 174 17.4
GP_EBOZM 336 – 352 15.84
GP_EBOZM 85 – 99 15.38
GP_EBOZM 238 – 252 13.8
GP_EBOZM 190 – 204 11.22
GP_EBOZM 555 – 569 10.5
GP_EBOZM 215 – 229 10.05
NOT SHOWN ON SCALE
iVax Analysis of Ebola virus Class II Analysis
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• EpiMatrix report of GP, cluster 16
• Homology search of GP, cluster 16 • Conserva1on among the Filoviridae genus (excluding Zaire
Ebolavirus – Mayinga), 15 maximum hits
iVax Analysis of Ebola virus Class II Analysis
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iVax Analysis of Ebola virus Class II Analysis
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• EpiMatrix report of GP, cluster 32
• Homology search of GP, cluster 32 • Conserva1on among the Filoviridae genus (excluding Zaire
Ebolavirus – Mayinga), 15 maximum hits
iVax Analysis of Ebola virus Class II Analysis
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iVax Analysis of Ebola virus Class II Analysis
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• EpiMatrix report of GP, cluster 85
• Homology search of GP, cluster 85 • Conserva1on among the Filoviridae genus (excluding Zaire
Ebolavirus – Mayinga), 15 maximum hits
iVax Analysis of Ebola virus Class II Analysis
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iVax Analysis of Ebola virus Class II Analysis
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• EpiMatrix report of GP, cluster 156
• Homology search of GP, cluster 156 • Conserva1on among the Filoviridae genus (excluding Zaire
Ebolavirus – Mayinga), 15 maximum hits
iVax Analysis of Ebola virus Class II Analysis
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iVax Analysis of Ebola virus Class II Analysis
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• EpiMatrix report of GP, cluster 190
• Homology search of GP, cluster 190 • Conserva1on among the Filoviridae genus (excluding Zaire
Ebolavirus – Mayinga), 15 maximum hits
iVax Analysis of Ebola virus Class II Analysis
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iVax Analysis of Ebola virus Class II Analysis
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• EpiMatrix report of GP, cluster 215
• Homology search of GP, cluster 215 • Conserva1on among the Filoviridae genus (excluding Zaire
Ebolavirus – Mayinga), 15 maximum hits
iVax Analysis of Ebola virus Class II Analysis
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iVax Analysis of Ebola virus Class II Analysis
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• EpiMatrix report of GP, cluster 238
• Homology search of GP, cluster 238 • Conserva1on among the Filoviridae genus (excluding Zaire
Ebolavirus – Mayinga), 15 maximum hits
iVax Analysis of Ebola virus Class II Analysis
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iVax Analysis of Ebola virus Class II Analysis
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• EpiMatrix report of GP, cluster 245
• Homology search of GP, cluster 245 • Conserva1on among the Filoviridae genus (excluding Zaire
Ebolavirus – Mayinga), 15 maximum hits
iVax Analysis of Ebola virus Class II Analysis
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iVax Analysis of Ebola virus Class II Analysis
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• EpiMatrix report of GP, cluster 336
• Homology search of GP, cluster 336 • Conserva1on among the Filoviridae genus (excluding Zaire
Ebolavirus – Mayinga), 15 maximum hits
iVax Analysis of Ebola virus Class II Analysis
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iVax Analysis of Ebola virus Class II Analysis
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• EpiMatrix report of GP, cluster 555
• Homology search of GP, cluster 555 • Conserva1on among the Filoviridae genus (excluding Zaire
Ebolavirus – Mayinga), 15 maximum hits
iVax Analysis of Ebola virus Class II Analysis
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iVax Analysis of Ebola virus Class II Analysis
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• EpiMatrix report of GP, cluster 566
• Homology search of GP, cluster 566 • Conserva1on among the Filoviridae genus (excluding Zaire
Ebolavirus – Mayinga), 15 maximum hits
iVax Analysis of Ebola virus Class II Analysis
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iVax Analysis of Ebola virus Class II Analysis
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• EpiMatrix report of GP, cluster 579
• Homology search of GP, cluster 579 • Conserva1on among the Filoviridae genus (excluding Zaire
Ebolavirus – Mayinga), 15 maximum hits
iVax Analysis of Ebola virus Class II Analysis
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Cluster EPX score
# epitopes TCR-‐facing residues conservaOon (1)
Human cross-‐reacOvity (2)
Microbiome cross-‐reacOvity (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 Analysis – Conservation wth Human etc.
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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-‐reac1vity analysis of GP clusters (JanusMatrix analysis)
Cluster EPX score
# epitopes TCR-‐facing residues conservaOon (1)
Human cross-‐reacOvity (2)
Microbiome cross-‐reacOvity (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 Analysis – Conservation wth Human etc.
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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-‐reac1vity analysis of GP clusters (JanusMatrix analysis)
• Zaire Ebolavirus – Mayinga surface protein, GP, has a low immunogenic poten1al at the protein level
• iVAX iden1fied 16 clusters of immunogenicity in the GP sequence
• Several clusters present: – High EpiMatrix scores – High degree of conserva1on among Filoviruses – Low degree of cross-‐reac1vity to human and human microbiome
sequences
iVax Analysis of Ebola virus Class II Analysis – Summary
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• Zaire Ebolavirus – Mayinga surface protein, GP, has a low immunogenic poten1al at the protein level
• iVAX iden1fied 16 clusters of immunogenicity in the GP sequence
• From these, three (Cluster 85, Cluster 150, and Cluster 555) present proper1es interes1ng for vaccine development: – High EpiMatrix scores – High degree of conserva1on among Filoviruses – Low degree of cross-‐reac1vity to human and human microbiome
sequences
iVax Analysis of Ebola virus Class II Analysis – Summary
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• EpiMatrix scores of Zaire Ebolavirus – Mayinga proteins (data parsed in 9-‐mers)
iVax Analysis of Ebola virus Class I Analysis
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• EpiMatrix scores of Zaire Ebolavirus – Mayinga proteins (data parsed in 10-‐mers)
iVax Analysis of Ebola virus Class I Analysis
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• Immunogenicity screening of Zaire Ebolavirus – Mayinga GP protein
• iVAX iden1fied 143 9-‐mers and 10-‐mers sequences with increased immunogenic poten1al in regards to at least one HLA Class I allele (HLA-‐A*0101, HLA-‐A*0201, HLA-‐A*0301, HLA-‐A*2402, HLA-‐B*0702, HLA-‐B*4403)
• From these, 80 sequences present limited homology to human sequences (less than 5 hits)
• From these, 59 sequences have at least one posi1ve hit and no nega1ve hit in IEDB
Please contact [email protected] for more informa1on.
iVax Analysis of Ebola virus Class I Analysis
8/17/14 non-‐non-‐confiden1al 64
• Immunogenicity screening of Zaire Ebolavirus – Mayinga GP protein
iVax Analysis of Ebola virus Class I Analysis for details email [email protected]
8/17/14 non-‐non-‐confiden1al 65
143 9-‐mers and 10-‐mers with increased immunogenic poten1al 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 posi1ve hit and no nega1ve hit in IEDB
(1) HLA-A*0101, HLA-A*0201, HLA-A*0301, HLA-A*2402, HLA-B*0702, HLA-B*4403
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
h^p://bit.ly/EpiPubs 67
Vish Mokashi Biswajit Biswas
Manon Cox Indresh Srivastava
Manabu Ato Yoshi Takahashi
Drew Hannaman