EpiVax_iVAX_Non_Confidential_June2014_BIO2014

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iVAX: A suite of cloud-based tools for epitope-based vaccine design from whole genomes. Also used to assess antigens for cross-reactivity (JanusMatrix) and to choose epitope-rich antigen candidates. iVAX reports available.

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EpiVax_iVAX_Non_Confidential_June2014_BIO2014

  1. 1. iVAX In Silico Vaccine Design BIO 2014, San Diego
  2. 2. • Biotech company based in Providence Rhode Island • Owned and operated by Annie De Groot and Bill Martin Who are We? (EpiVax) EpiVax designs and develops safer, more effective biologic products and vaccines Engaged “To improve human health everywhere” Cutting Edge Continuously innovating Trusted Pharma- and Peer- approved EpiVax - Non-Confidential 2
  3. 3. http://bit.ly/EpiPubs 3 iVAX Toolkit – Commercial EpiVax - Non-Confidential
  4. 4. iVAX Toolkit – Academic 4
  5. 5. Active Collaborators / Vaccines Bill Martin Lenny Moise Frances Terry Leslie Cousens Ryan Tassone Howie Latimer Mindy Cote Lauren Levitz Christine Boyle Alan Rothman Carey Medin Andres Guitierrez Danielle Aguirre Joe Desrosiers Thomas Mather Wendy Coy Loren Fast 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 5
  6. 6. iVAX – Quick Facts • Comprehensive set of vaccine design tools • Tools to engineer maximal immunogenicity • Applications to assay reagent development and diagnostics • Interactive and user friendly • 24/7 access • On-site training program • Technical support service EpiVax - Non-Confidential 6
  7. 7. 7EpiVax - Non-Confidential Vaccine Design Tools and Techniques
  8. 8. 8 • EpiMatrix – maps T cell epitopes • ClustiMer - Promiscuous / supertype epitopes • BlastiMer - Avoiding “self” - autoimmunity • Conservatrix – Identifies Conserved Segments • JanusMatrix – Identifies T cell cross-reactivity • EpiAssembler – Immunogenic consensus sequences • Aggregatrix – Optimizing the coverage of vaccines • VaxCAD - Processing and assembly iVAX Fully integrated From genome to vaccine Seamless Vaccine Design Integrated toolkit is unique to iVax EpiVax - Non-Confidential
  9. 9. Strain 1 Strain 3 Strain 2 core genome dispensable genes strain-specific genespangenome Comparative Genomics Impacts Vaccine Immunogen Selection EpiVax - Non-Confidential 9
  10. 10. 11 EpiMatrix T cell epitopes are linear and directly derived from antigen sequence Binding is determined by amino acid side chains (R groups) and ‘encoded’ in single letter code Mature APC Protein MHC II Pocket Peptide Epitope • EpiMatrix maps putative epitopes – matrix based prediction algorithm using pocket profile method described by Sturniolo and Hammer • Predict likelihood of sequence binding to HLA I and II EpiVax - Non-Confidential
  11. 11. EpiVax HLA “Supertype” Coverage • EpiVax tests for binding potential to the most common HLA molecules within each of the “supertypes” shown to the left. • This allows us to provide results that are representative of >90% of human populations worldwide* without the necessity of testing each haplotype individually. 12 * Southwood et. al., Several Common HLA-DR Types Share Largely Overlapping Peptide Binding Repertoires. 1998. Journal of Immunology. EpiVax - Non-Confidential
  12. 12. Epitope Identification EpiMatrix is the best available epitope discovery tool 13 De Groot and Martin. Reducing risk, improving outcomes: Bioengineering less immunogenic protein therapeutics. Clinical Immunology 2009. 131, 189-201. EpiVax - Non-Confidential
  13. 13. EpiVax - Non-Confidential 14 ClustiMer 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
  14. 14. 15 Identifying the most conserved 9-mers allows for protection against more strains with fewer epitopes Conservatrix Finds Conserved 9-mers Conserved epitope CTRPNNTRK CTRPNNTRK CTRPNNTRK CTRPNNTRK CTRPNNTRK CTRPNNTRK CTRPNNTRK EpiVax - Non-Confidential
  15. 15. STRAIN 01 Q X S W P K V E Q F W A K H X W N X I S X I Q Y L STRAIN 02 Q A S W P K V E X F W A K H M W N F I S G I Q Y L STRAIN 03 Q X S W P K X E Q F W A K H M W N F I S G I Q Y X STRAIN 04 Q A S W X K V E Q F W A K H M W N F X S X I Q Y L STRAIN 05 Q X S W P K V E Q F W A K H M W N F I S G I Q Y L STRAIN 06 Q A S W P K X E Q F W A X H M W N F I S G I Q Y X STRAIN 07 Q X S W P K V E Q F W A K H M X N F I S G I Q Y L STRAIN 08 Q A S W X K V E Q F W A K H M W N F I S G I Q Y L STRAIN 09 Q X S W P K X E Q F W A K H M W N F X S X I X Y X STRAIN 10 Q A S W P R V E Q F W A K H M W N F I X G I Q Y L STRAIN 11 Q A S W P K V E Q F W A K H M W N F I S G I Q Y L STRAIN 12 Q A S W X K V E Q F W A X H M W N F I S G I Q Y X STRAIN 13 Q A S W P K V E Q F W A K H M W N F I S G I Q Y L STRAIN 14 Q A S W X K X E Q F W A K H M W N F I S X I Q Y L STRAIN 15 Q A S W P K V E X F W X K H M W N F I S G I Q Y L STRAIN 16 Q X S W P K V E Q F W A K H M W N F I X G I Q Y L STRAIN 17 X A S W X K V E Q F W A K H M W N F I S G I Q Y X STRAIN 18 Q X S W P K X E Q F W A K H M W N X I S G I Q Y L STRAIN 19 Q A S W X K V E Q F W A K H M W N F I S X I Q Y L STRAIN 20 Q A S W P K V E Q F W A X H M W N F I S G I Q Y L x F W A K H M W N F W P K V E Q F W A Q A S W P K V E Q N F I S G I Q Y L M W N F I S G I Q Q A S W P K V E Q F W A K H M W N F I S G I Q Y L EpiAssembler Produces Immunogenic Consensus Sequences
  16. 16. VaccineCAD VaxCAD will identify junctional epitopes and rearrange chosen epitopes to reduce junctional epitope formation EpiVax - Non-Confidential 17
  17. 17. 18 -10 0 10 20 30 40 50 HP4117 HP4179 HP4007 HP4111 HP4018 HP4070 HP4034 HP4193 HP4065 HP4181 HP4157 HP4060 HP4068 HP4164 HP4160 HP4175 HP4127 HP4120 HP4126 HP4154 HP4168 HP4119 HP4100 HP4001 HP4061 EpiMatrixClusterScore Peptides in Default order in construct HP_IIB Epitope Cluster Score Junctional Cluster Score -10 0 10 20 30 40 50 HP4117 HP4061 HP4181 HP4111 HP4018 HP4070 HP4060 HP4157 HP4065 HP4001 HP4193 HP4034 HP4068 HP4168 HP4160 HP4175 HP4127 HP4126 HP4007 HP4154 HP4164 HP4119 HP4100 HP4120 HP4179 EpiMatrixClusterScore Peptides in Optimized order in construct HP_IIB Epitope Cluster Score Junctional Cluster Score VaccineCAD VaccineCAD Eliminates Introduced Junctional Epitopes EpiVax - Non-Confidential
  18. 18. 19 But Wait! Exclude Epitopes In all of our vaccines we eliminate cross-reactive epitopes SelfForeign EpiVax - Non-Confidential
  19. 19. Human PathogenHuman Microbiome Protective epitopes Potentially detrimental cross- reactive epitopes Potentially detrimental cross- reactive epitopes Epitope Cross-Reactivity Impacts Vaccine Immunogen Selection EpiVax - Non-Confidential 20
  20. 20. MHC TCR A New Way to Analyze Homology: JanusMatrix JanusMatrix is designed to predict the potential for cross reactivity between epitope clusters and the human genome, based on conservation of TCR-facing residues in their putative HLA ligands. EpiVax - Non-Confidential 21
  21. 21. VLQSSGLSYS ( T cell epitope) FLQDSNLYK (T cell epitope with same TCR face) Another human protein A different human protein A human protein Source protein Predicted 9-mer epitope from a source protein Human protein where cross-reactive epitopes are present 9-mer from human prevalent proteome, 100% TCR face identical to source epitope Source Protein or large peptide JanusMatrix Cross-reactivity Networks 22EpiVax - Non-Confidential
  22. 22. HCV_G1_1605 HCV_G1_DEXDC_1246 HCV_G1_NS5A_1988 HCV_G1_NS4B_1725 HCV_G1_2898 HCV_G1_2913 HCV_G1_ENV_359 HCV_G1_2941 HCV_G1_NS4B_1910 HCV_G1_ENV_255 HCV_G1_2440 HCV_G1_NS2_732 HCV_G1_NS2_748 HCV_G1_2840 HCV_G1_1941 HCV_G1_NS4B_1769 HCV_G1_NS2_909 HCV_G1_2485 HCV_G1_NS4b_1798 HCV_G1_NS4B_1790 HCV_G1_NS4B_1876 HCV_G1_2879 All induced Teff response Example: HCV Vaccine 22/23 epitopes vs. human proteome 23EpiVax - Non-Confidential
  23. 23. 646897107 LRHM_1393 fibronectin-binding protein [Lactobacillus rhamnosus GG, ATCC 53103] 644328538 HMPREF0530_2361 fibronectin binding protein A [Lactobacillus paracasei ATCC 25302] 643123048 BACDOR_03958 ABC-type multidrug transport system, ATPase and permease components [Bacteroides dorei DSM 17855] 643926407 Lparp8_010100002015 fibronectin-binding protein [Lactobacillus paracasei 8700:2] 644392137 HMPREF0539_1504 fibronectin binding protein A [Lactobacillus rhamnosus LMS2-1] 650063005 HMPREF0864_03563 PTS protein [Enterobacteriaceae bacterium 9_2_54FAA] 650576916 CK1_14550 hypothetical protein [Ruminococcus sp. SR1/5] 643138141 DESPIG_00923 Glycogen debranching enzyme [Desulfovibrio piger ATCC 29098] 650018804 HMPREF1004_00251 twin-arginine translocation pathway signal [Ralstonia sp. 5_7_47FAA] 645282591 B2_010100019185 hypothetical protein [Bacteroides sp. 2_1_7] 648908601 HMPREF9008_03392 RagB/SusD hypothetical protein [Bacteroides sp. 20_3] 648889725 HMPREF0104_03558 RagB/SusD domain-containing protein [Bacteroides sp. 3_1_19] 643155446 PRABACTJOHN_01075 RagB, SusD and hypothetical proteins. [Parabacteroides johnsonii DSM 18315] 646289358 HMPREF0619_03868 conserved hypothetical protein [Parabacteroides sp. D13] 650533738 CLS_16740 TRAP transporter, DctM subunit [Clostridium cf. saccharolyticum K10]651551911 HMPREF9538_05675 LysR substrate binding domain protein [Klebsiella sp. MS 92-3] 647938759 HMPREF0485_01635 transcription regulator protein, MDR efflux pump cluster [Klebsiella sp. 1_1_55] 651312886 HMPREF0240_01840 shikimate kinase [Clostridium sp. D5] 650592773 CL3_32810 TRAP transporter, DctM subunit [Clostridiales sp. SM4/1] 643916645 Cbac1_010100015578 PTS system, IIB component [Clostridiales sp. 1_7_47FAA] 648576449 HMPREF9541_02931 conserved hypothetical protein [Escherichia coli MS 116-1] 643917888 Cbac1_010100021787 hypothetical protein [Clostridiales sp. 1_7_47FAA] 646213459 BSBG_01768 ABC transporter ATP-binding protein [Bacteroides sp. 9_1_42FAA] 647369118 EDWATA_01849 threonine-phosphate decarboxylase [Edwardsiella tarda ATCC 23685] 650063271 HMPREF0864_03827 UDP-N-acetylglucosamine diphosphorylase/glucosamine-1-phosphate N-acetyltransferase [Enterobacteriaceae bacterium 9_2_54FAA] 644328486 HMPREF0530_2309 ATP-dependent deoxyribonuclease, subunit A [Lactobacillus paracasei ATCC 25302] 647855848 HMPREF0847_00391 hypothetical protein [Streptococcus sp. 2_1_36FAA] 644392182 HMPREF0539_1549 ATP-dependent deoxyribonuclease, subunit A [Lactobacillus rhamnosus LMS2-1] 647369715 EDWATA_02446 integral membrane protein [Edwardsiella tarda ATCC 23685] 646897150 LRHM_1436 ATP-dependent exonuclease subunit A [Lactobacillus rhamnosus GG, ATCC 53103] 643926359 Lparp8_010100001765 ATP-dependent exoDNAse (exonuclease V) beta subunit [Lactobacillus paracasei 8700:2] 651373768 HMPREF0127_04622 hypothetical protein [Bacteroides sp. 1_1_30] 648881902 HMPREF9007_00606 RNA polymerase ECF-type sigma factor [Bacteroides sp. 1_1_14] 648892415 HMPREF0106_01939 RNA polymerase ECF-type sigma factor [Bacteroides sp. D22] 647459210 CW1_1639 RNA polymerase sigma-70 factor [Bacteroides ovatus SD CC 2a] 646275464 BSIG_02296 RNA polymerase ECF-type sigma factor [Bacteroides sp. 1_1_6] 644270816 ROSEINA2194_02314 TrpR-related protein YerC/YecD [Roseburia inulinivorans DSM 16841] 651312216 HMPREF0240_01166 TrpR-like protein [Clostridium sp. D5] 651333144 HMPREF0988_02534 hypothetical protein [Lachnospiraceae bacterium 1_4_56FAA] 651346833 HMPREF0993_02418 hypothetical protein [Lachnospiraceae bacterium 5_1_57FAA] 650583643 RTO_16000 TrpR-related protein YerC/YecD [Ruminococcus torques L2-14] 651366495 HMPREF1025_00393 TrpR protein YerC/YecD [Lachnospiraceae bacterium 3_1_46FAA] 650577568 CK1_22230 TrpR-related protein YerC/YecD [Ruminococcus sp. SR1/5] 650567742 ROI_38070 TrpR-related protein YerC/YecD [Roseburia intestinalis M 50/1] 651343264 HMPREF0994_05806 hypothetical protein [Lachnospiraceae bacterium 3_1_57FAA_CT1] 650570318 RO1_26580 TrpR-related protein YerC/YecD [Roseburia intestinalis XB6B4] 644156939 RUMHYD_02612 TrpR-related protein YerC/YecD [Blautia hydrogenotrophica DSM 10507] 651328108 HMPREF0990_00344 TrpR protein YerC/YecD [Lachnospiraceae bacterium 1_1_57FAA] 650580572 CK5_17800 TrpR-related protein YerC/YecD [Ruminococcus obeum A2-162] 650047371 HMPREF1026_00070 TrpR/YerC/YecD protein [Lachnospiraceae bacterium sp. 8_1_57FAA] 643112515 CLONEX_00021 TrpR-related protein YerC/YecD [Clostridium nexile DSM 1787] 650538389 CC1_32850 TrpR-related protein YerC/YecD [Coprococcus catus GD/7] 644101358 COPCOM_01077 TrpR-related protein YerC/YecD [Coprococcus comes ATCC 27758] 651337064 HMPREF0991_03195 hypothetical protein [Lachnospiraceae bacterium 2_1_58FAA] 650042220 HMPREF1016_01813 dolichyl-phosphate-mannose-protein mannosyltransferase [Bacteroides eggerthii 1_2_48FAA] 650528931 BIL_14850 hypothetical protein [Bifidobacterium longum longum F8] 647513128 HMPREF0493_1391 cytidylate kinase [Lactobacillus amylolyticus DSM 11664] 644165764 BACCELL_00927 4-amino-4-deoxy-L-arabinose transferase and related glycosyltransferases of PMT family [Bacteroides cellulosilyticus DSM 14838] 644284103 HMPREF0496_0349 adenylylsulfate reductase [Lactobacillus brevis gravesensis ATCC 27305] 651542515 HMPREF9446_00260 dolichyl-phosphate-mannose-protein mannosyltransferase [Bacteroides fluxus YIT 12057] 644158474 HOLDEFILI_00216 Predicted transcriptional regulators [Holdemania filiformis VPI J1-31B-1, DSM 12042] 646262918 HRAG_00601 thymidylate kinase [Helicobacter bilis ATCC 43879]643140215 DESPIG_02998 His Kinase A (phosphoacceptor) domain./Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase. [Desulfovibrio piger ATCC 29098] 643145692 PROVALCAL_01369 Transcriptional regulator [Providencia alcalifaciens DSM 30120] 648927374 HMPREF0326_02088 type VI secretion protein, VC_A0114 family [Desulfovibrio sp. 3_1_syn3] 651541957 HMPREF9445_03033 dolichyl-phosphate-mannose-protein mannosyltransferase [Bacteroides clarus YIT 12056] 643095437 BACEGG_00204 4-amino-4-deoxy-L-arabinose transferase and related glycosyltransferases of PMT family [Bacteroides eggerthii DSM 20697] 650569022 RO1_11940 hypothetical protein [Roseburia intestinalis XB6B4] 650087839 HMPREF9464_01029 hypothetical protein [Sutterella wadsworthensis 3_1_45B] 644159799 HOLDEFILI_01543 hypothetical protein [Holdemania filiformis VPI J1-31B-1, DSM 12042] 651361870 HMPREF1018_00744 hypothetical protein [Bacteroides sp. 2_1_56FAA] 651383622 HMPREF9477_00885 hypothetical protein [Lachnospiraceae bacterium 2_1_46FAA] 646269512 BSHG_00932 conserved hypothetical protein [Bacteroides sp. 3_2_5] 651312463 HMPREF0240_01414 AMP-dependent synthetase and ligase [Clostridium sp. D5] 644160607 HOLDEFILI_02351 Na -driven multidrug efflux pump [Holdemania filiformis VPI J1-31B-1, DSM 12042] 647885571 HMPREF0101_02623 conserved hypothetical protein [Bacteroides sp. 2_1_16] 651567871 HMPREF9413_2216 Beta-eliminating lyase [Paenibacillus sp. HGF7] 650538330 CC1_32230 ATPase, P-type (transporting), HAD superfamily, subfamily IC [Coprococcus catus GD/7] 650045277 HMPREF1023_00949 luxR family Bacterial regulatory protein [Eggerthella sp. 1_3_56FAA] 643925771 HpulM9_010100009425 thymidylate kinase [Helicobacter pullorum MIT 98-5489] 643140200 DESPIG_02983 hypothetical protein [Desulfovibrio piger ATCC 29098] 650571179 RO1_37110 tRNA(Ile)-lysidine synthetase, N-terminal domain/tRNA(Ile)-lysidine synthetase, C-terminal domain [Roseburia intestinalis XB6B4] 646006646 BacD2_010100019909 hypothetical protein [Bacteroides sp. D2] 651516796 HMPREF9412_0783 Beta-eliminating lyase [Paenibacillus sp. HGF5] 646224770 BSCG_03288 conserved hypothetical protein [Bacteroides sp. 2_2_4] 647880008 HMPREF0102_01882 conserved hypothetical protein [Bacteroides sp. 2_1_22] 647460066 CW1_4644 conserved domain protein [Bacteroides ovatus SD CC 2a] 646219274 BSAG_02634 conserved hypothetical protein [Bacteroides sp. D1] 648905787 HMPREF9010_03609 conserved hypothetical protein [Bacteroides sp. 3_1_23] 647442302 CW3_4406 conserved domain protein [Bacteroides xylanisolvens SD CC 1b] 647455517 CUY_1326 conserved hypothetical protein [Bacteroides ovatus SD CMC 3f] 648890757 HMPREF0106_00282 hypothetical protein [Bacteroides sp. D22] 648564978 HMPREF9530_02421 iron chelate uptake ABC transporter, FeCT family, permease protein [Escherichia coli MS 21-1] 648597116 HMPREF9549_02183 iron chelate uptake ABC transporter, FeCT family, permease protein [Escherichia coli MS 185-1] 648552428 HMPREF9534_00065 iron chelate uptake ABC transporter, FeCT family, permease protein [Escherichia coli MS 69-1] 648547530 HMPREF9531_00512 iron chelate uptake ABC transporter, FeCT family, permease protein [Escherichia coli MS 45-1] 650543286 ENC_32680 ABC-type Fe3 -siderophore transport system, permease component [Enterobacter cloacae cloacae NCTC 9394] 646207500 ESAG_01227 iron ABC transporter permease [Escherichia sp. 3_2_53FAA] 648588094 HMPREF9553_04319 iron chelate uptake ABC transporter, FeCT family, permease protein [Escherichia coli MS 200-1] 648590015 HMPREF9551_00793 iron chelate uptake ABC transporter, FeCT family, permease protein [Escherichia coli MS 196-1] 646243637 CSAG_00020 predicted protein [Citrobacter sp. 30_2] 650087745 HMPREF9464_00950 crp/Fnr family Transcriptional regulator [Sutterella wadsworthensis 3_1_45B] 650539665 CCU_15010 hypothetical protein [Coprococcus sp. ART55/1] 650013489 HMPREF0983_02062 putative diarrheal toxin [Erysipelotrichaceae bacterium sp. 3_1_53] 650320841 HMPREF9420_2035 conserved hypothetical protein [Prevotella salivae DSM 15606] 651572855 HMPREF9413_5814 arylsulfatase [Paenibacillus sp. HGF7] 650045118 HMPREF1023_00790 luxR family Bacterial regulatory protein [Eggerthella sp. 1_3_56FAA] 650061657 HMPREF0864_02232 alpha amylase [Enterobacteriaceae bacterium 9_2_54FAA] 650352274 HMPREF9443_02055 CRISPR-associated protein, Csn1 family [Phascolarctobacterium sp. YIT 12067] 644226848 EUBHAL_01293 Phosphate starvation-inducible protein PhoH, predicted ATPase [Eubacterium hallii DSM 3353] 651360094 HMPREF1017_04090 hypothetical protein [Bacteroides ovatus 3_8_47FAA] 646224828 BSCG_03346 conserved hypothetical protein [Bacteroides sp. 2_2_4] 646259551 OFAG_01507 chaperone SurA [Oxalobacter formigenes HOxBLS] 647449747 CUW_1263 DNA topoisomerase IV, A subunit [Turicibacter sanguinis PC909] 648587459 HMPREF9553_03683 hypothetical protein [Escherichia coli MS 200-1] 644097630 PROPEN_02340 AAA domain (Cdc48 subfamily). [Proteus penneri ATCC 35198] 646247184 CSAG_03511 Sua5/YciO/YrdC/YwlC family protein [Citrobacter sp. 30_2] 643139396 DESPIG_02179 Outer membrane protein (OmpH-like). [Desulfovibrio piger ATCC 29098] 650088265 HMPREF9464_01439 flp pilus assembly protein [Sutterella wadsworthensis 3_1_45B] 644270805 ROSEINA2194_02303 Serine/threonine protein kinase [Roseburia inulinivorans DSM 16841] 646035840 ChatD1_010100007516 hypothetical protein [Clostridium hathewayi DSM 13479] 650598591 CK3_33190 TrpR-related protein YerC/YecD [Clostridiales sp. SS3/4] 644177756 CLOSTASPAR_02371 TrpR-related protein YerC/YecD [Clostridium asparagiforme DSM 15981] 651517389 HMPREF9412_5440 transcriptional regulator, LuxR family [Paenibacillus sp. HGF5] 643917094 Cbac1_010100017829 TrpR like protein, YerC/YecD [Clostridiales sp. 1_7_47FAA]651678006 HMPREF9418_0568 transcriptional regulator Anr [Neisseria macacae ATCC 33926] 646304999 HMPREF0026_02442 primosomal protein N [Acinetobacter junii SH205] 643098504 BACEGG_03273 Mg-dependent DNase [Bacteroides eggerthii DSM 20697] 650537523 CC1_22940 Uncharacterized conserved protein (some members contain a von Willebrand factor type A (vWA) domain) [Coprococcus catus GD/7] 650041378 HMPREF1016_00978 Mg-dependent DNase [Bacteroides eggerthii 1_2_48FAA] 648688861 HMPREF9521_00708 histidine kinase [Enterococcus faecalis TX2134] 647988365 HMPREF0874_00617 methylmalonyl-CoA epimerase [Veillonella sp. 6_1_27] 644294383 HMPREF0348_1204 possible histidine kinase [Enterococcus faecalis TX0104] 650588611 ENT_26790 Signal transduction histidine kinase [Enterococcus sp. 7L76] 645347505 ShiD9_010100016841 cell wall shape-determining protein [Shigella sp. D9] 648572234 HMPREF9535_03818 rod shape-determining protein RodA [Escherichia coli MS 78-1] 648531274 HMPREF9536_05721 rod shape-determining protein RodA [Escherichia coli MS 84-1] 651549390 HMPREF9538_03152 rod shape-determining protein RodA [Klebsiella sp. MS 92-3] 648541752 HMPREF9548_05239 rod shape-determining protein RodA [Escherichia coli MS 182-1] 648577976 HMPREF9541_04458 rod shape-determining protein RodA [Escherichia coli MS 116-1] 648556685 HMPREF9534_04323 rod shape-determining protein RodA [Escherichia coli MS 69-1] 648535600 HMPREF9540_04218 rod shape-determining protein RodA [Escherichia coli MS 115-1] 648598735 HMPREF9549_03804 rod shape-determining protein RodA [Escherichia coli MS 185-1] 646206839 ESAG_00573 rod shape-determining protein RodA [Escherichia sp. 3_2_53FAA] 648927142 HMPREF0326_01859 RNA modification enzyme, MiaB-family [Desulfovibrio sp. 3_1_syn3] 646261147 OFBG_00955 FAD/FMN-containing dehydrogenase [Oxalobacter formigenes OXCC13] 644209508 CLOSTMETH_03465 Predicted Zn peptidase [Clostridium methylpentosum R2, DSM 5476] 646265889 HWAG_01253 conserved hypothetical protein [Helicobacter winghamensis ATCC BAA-430] 650351527 HMPREF9443_01307 L-asparaginase [Phascolarctobacterium sp. YIT 12067] 643124383 ANHYDRO_00256 Cna protein B-type domain. [Anaerococcus hydrogenalis DSM 7454] 644098715 PROPEN_03428 translation factor SUA5 [Proteus penneri ATCC 35198] 651546256 HMPREF9538_00017 negative regulator of genetic competence ClpC/MecB [Klebsiella sp. MS 92-3] 651337471 HMPREF0994_00057 hypothetical protein [Lachnospiraceae bacterium 3_1_57FAA_CT1] 647986504 HMPREF0873_00628 methylmalonyl-CoA epimerase [Veillonella sp. 3_1_44] 648531805 HMPREF9540_00421 ATPase family protein [Escherichia coli MS 115-1] 650020839 HMPREF1004_02304 ATP-dependent Clp protease, ATP-binding subunit ClpC [Ralstonia sp. 5_7_47FAA] 650319738 HMPREF9420_0951 conserved hypothetical protein [Prevotella salivae DSM 15606] 651342555 HMPREF0994_05103 hypothetical protein [Lachnospiraceae bacterium 3_1_57FAA_CT1] 648534834 HMPREF9540_03452 ATPase family protein [Escherichia coli MS 115-1] 646266598 ESCG_01087 ATPase with chaperone activity [Escherichia sp. 1_1_43] 648583660 HMPREF9547_04869 rod shape-determining protein RodA [Escherichia coli MS 175-1] 648551221 HMPREF9531_04206 rod shape-determining protein RodA [Escherichia coli MS 45-1] 645350729 E4_010100010287 cell wall shape-determining protein [Escherichia sp. 4_1_40B] 648588765 HMPREF9553_04990 rod shape-determining protein RodA [Escherichia coli MS 200-1] 647939288 HMPREF0485_02161 rod shape-determining protein RodA [Klebsiella sp. 1_1_55] 648593936 HMPREF9551_04716 rod shape-determining protein RodA [Escherichia coli MS 196-1] 648561740 HMPREF9550_03789 rod shape-determining protein RodA [Escherichia coli MS 187-1] 648565362 HMPREF9530_02805 rod shape-determining protein RodA [Escherichia coli MS 21-1] 646244048 CSAG_00429 cell wall shape-determining protein [Citrobacter sp. 30_2] 648524970 HMPREF9552_05139 rod shape-determining protein RodA [Escherichia coli MS 198-1] 644160019 HOLDEFILI_01763 Predicted transcriptional regulators [Holdemania filiformis VPI J1-31B-1, DSM 12042] 643922089 HcinC1_010100003150 hypothetical protein [Helicobacter cinaedi CCUG 18818] 647371096 EDWATA_03829 dipeptide ABC transporter, ATP-binding protein DppD [Edwardsiella tarda ATCC 23685] 650021631 HMPREF1004_03094 DNA polymerase III subunit alpha [Ralstonia sp. 5_7_47FAA] 647513266 HMPREF0493_1501 hypothetical protein [Lactobacillus amylolyticus DSM 11664] 646896283 LRHM_0608 putative multidrug ABC transporter ATP-binding component [Lactobacillus rhamnosus GG, ATCC 53103] 650062929 HMPREF0864_03487 yrdC domain-containing protein [Enterobacteriaceae bacterium 9_2_54FAA] 648926945 HMPREF0326_01668 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase [Desulfovibrio sp. 3_1_syn3] 644316707 HMPREF0545_1139 ribonuclease HI [Lactobacillus salivarius HO66, ATCC 11741] 650012947 HMPREF0983_01497 putative aspartate aminotransferase [Erysipelotrichaceae bacterium sp. 3_1_53] 644102280 COPCOM_02000 Transcriptional regulators [Coprococcus comes ATCC 27758] 643147789 PROVALCAL_03476 Predicted membrane protein [Providencia alcalifaciens DSM 30120] 647857524 HMPREF0847_02056 ATP-binding transporter ComA [Streptococcus sp. 2_1_36FAA] 650073316 HMPREF9488_01292 ABC transporter [Coprobacillus sp. 29_1] 650565850 ROI_15910 tRNA(Ile)-lysidine synthetase, N-terminal domain/tRNA(Ile)-lysidine synthetase, C-terminal domain [Roseburia intestinalis M 50/1] 643116437 CLONEX_03946 ABC-type nitrate/sulfonate/bicarbonate transport system, ATPase component [Clostridium nexile DSM 1787] 643139916 DESPIG_02699 GTP cyclohydrolase subunit MoaA [Desulfovibrio piger ATCC 29098] 651516013 HMPREF9412_5193 transcriptional regulator, AraC family [Paenibacillus sp. HGF5] 644143876 BACCOPRO_00205 Uncharacterized conserved protein [Bacteroides coprophilus DSM 18228] 651367701 HMPREF1025_01578 hypothetical protein [Lachnospiraceae bacterium 3_1_46FAA] 643928977 Lparp8_010100014860 tetracycline resistance structural protein TetA [Lactobacillus paracasei 8700:2] 644095308 PROPEN_00011 Arabinose efflux permease [Proteus penneri ATCC 35198] 643113002 CLONEX_00508 Arabinose efflux permease [Clostridium nexile DSM 1787] 648520000 HMPREF9552_00166 transporter, major facilitator family protein [Escherichia coli MS 198-1] 643923830 HcinC1_010100012020 tetracycline resistance structural protein TetA [Helicobacter cinaedi CCUG 18818] 643137611 DESPIG_00391 Arabinose efflux permease [Desulfovibrio piger ATCC 29098] 643158899 PRABACTJOHN_04529 Arabinose efflux permease [Parabacteroides johnsonii DSM 18315] 648579514 HMPREF9547_00720 transporter, major facilitator family protein [Escherichia coli MS 175-1] 643919673 Cbac1_010100030692 tetracycline resistance structural protein TetA [Clostridiales sp. 1_7_47FAA] 643147537 PROVALCAL_03223 Predicted membrane protein [Providencia alcalifaciens DSM 30120] 650060234 HMPREF0864_00824 sulfatase [Enterobacteriaceae bacterium 9_2_54FAA] 650353954 HMPREF9444_01560 conserved domain protein [Succinatimonas hippei YIT 12066] 646272574 BSHG_03947 conserved hypothetical protein [Bacteroides sp. 3_2_5] 650008741 HMPREF1007_00969 hypothetical protein [Bacteroides sp. 4_1_36] 650560164 FPR_30930 Restriction endonuclease S subunits [Faecalibacterium prausnitzii SL3/3] 650087089 HMPREF9464_00302 polar amino acid ABC transporter [Sutterella wadsworthensis 3_1_45B] 648534633 HMPREF9540_03250 peptidase, M48 family [Escherichia coli MS 115-1] 646227427 BSCG_05908 tetracycline resistance protein [Bacteroides sp. 2_2_4] 646216467 BSBG_04744 tetracycline resistance protein [Bacteroides sp. 9_1_42FAA] 648545499 HMPREF9543_03552 transporter, major facilitator family protein [Escherichia coli MS 146-1] 643911330 BbifN4_010100009360 tetracycline resistance structural protein TetA [Bifidobacterium bifidum NCIMB 41171] 645283147 B2_010100021971 tetracycline resistance protein [Bacteroides sp. 2_1_7] 643913320 BloniC5_010100009852 tetracycline resistance structural protein TetA [Bifidobacterium longum longum CCUG 52486] 644288259 HMPREF0497_1383 conserved hypothetical protein [Lactobacillus buchneri ATCC 11577]648538536 HMPREF9548_02020 transporter, major facilitator family protein [Escherichia coli MS 182-1] 644100297 COPCOM_00016 Arabinose efflux permease [Coprococcus comes ATCC 27758] 646228165 BSEG_00669 ABC transporter ATP-binding protein [Bacteroides dorei 5_1_36/D4] 644286383 HMPREF0496_2581 conserved hypothetical protein [Lactobacillus brevis gravesensis ATCC 27305] 651363233 HMPREF1018_02096 hypothetical protein [Bacteroides sp. 2_1_56FAA] 646240811 MBAG_00648 predicted protein [Coprobacillus sp. D7] 647893735 HMPREF9024_01405 transcription accessory protein [Pediococcus acidilactici 7_4] 644156633 RUMHYD_02306 Pyruvate:ferredoxin oxidoreductase and related 2-oxoacid:ferredoxin oxidoreductases, gamma subunit [Blautia hydrogenotrophica DSM 10507] 650198262 HMPREF0623_0974 YhgF like protein [Pediococcus acidilactici DSM 20284] 647457612 CW1_2658 efflux ABC transporter, permease protein [Bacteroides ovatus SD CC 2a] 645345968 ShiD9_010100009122 hypothetical protein [Shigella sp. D9] 646267454 ESCG_00515 conserved hypothetical protein [Escherichia sp. 1_1_43] 648588066 HMPREF9553_04291 hypothetical protein [Escherichia coli MS 200-1] 651357900 HMPREF1017_01928 hypothetical protein [Bacteroides ovatus 3_8_47FAA] 648597143 HMPREF9549_02210 conserved hypothetical protein [Escherichia coli MS 185-1] 648538381 HMPREF9548_01865 hypothetical protein [Escherichia coli MS 182-1] 646207525 ESAG_01252 conserved hypothetical protein [Escherichia sp. 3_2_53FAA] 647456123 CW1_3815 efflux transporter, outer membrane factor lipoprotein, NodT family [Bacteroides ovatus SD CC 2a] 648582903 HMPREF9547_04111 hypothetical protein [Escherichia coli MS 175-1] 651369358 HMPREF0127_00262 hypothetical protein [Bacteroides sp. 1_1_30] 648529403 HMPREF9536_03850 hypothetical protein [Escherichia coli MS 84-1] 651373678 HMPREF0127_04532 hypothetical protein [Bacteroides sp. 1_1_30] 648589991 HMPREF9551_00769 conserved hypothetical protein [Escherichia coli MS 196-1] 648569110 HMPREF9535_00693 conserved hypothetical protein [Escherichia coli MS 78-1] 646895903 LRHM_0232 conserved hypothetical protein [Lactobacillus rhamnosus GG, ATCC 53103] 644328023 HMPREF0530_1852 conserved hypothetical protein [Lactobacillus paracasei ATCC 25302] 643927741 Lparp8_010100008715 Predicted membrane protein [Lactobacillus paracasei 8700:2] 647856891 HMPREF0847_01428 GNAT family acetyltransferase [Streptococcus sp. 2_1_36FAA] 644391441 HMPREF0539_0815 permease [Lactobacillus rhamnosus LMS2-1] 644390750 HMPREF0539_0126 permease [Lactobacillus rhamnosus LMS2-1] 647453271 CUY_5065 efflux transporter, outer membrane factor lipoprotein, NodT family [Bacteroides ovatus SD CMC 3f] 646227380 BSCG_05865 outer membrane efflux protein oprM [Bacteroides sp. 2_2_4] 648903495 HMPREF9010_01082 outer membrane efflux protein OprM [Bacteroides sp. 3_1_23] 648894940 HMPREF0106_04483 outer membrane efflux protein OprM [Bacteroides sp. D22] 646220831 BSAG_04177 outer membrane efflux protein oprM [Bacteroides sp. D1] 646007548 BacD2_010100024426 outer membrane efflux protein oprM precursor [Bacteroides sp. D2] 647879744 HMPREF0102_01619 outer membrane efflux protein oprM [Bacteroides sp. 2_1_22] 647442660 CW3_4757 efflux transporter, outer membrane factor lipoprotein, NodT family [Bacteroides xylanisolvens SD CC 1b] 648562067 HMPREF9550_04116 conserved hypothetical protein [Escherichia coli MS 187-1] 645351388 E4_010100013599 hypothetical protein [Escherichia sp. 4_1_40B] 648547556 HMPREF9531_00538 conserved hypothetical protein [Escherichia coli MS 45-1] 648532122 HMPREF9540_00738 conserved hypothetical protein [Escherichia coli MS 115-1] 648525212 HMPREF9552_05381 conserved hypothetical protein [Escherichia coli MS 198-1] 648577642 HMPREF9541_04124 conserved hypothetical protein [Escherichia coli MS 116-1] 648552447 HMPREF9534_00084 conserved hypothetical protein [Escherichia coli MS 69-1] 648564996 HMPREF9530_02439 conserved hypothetical protein [Escherichia coli MS 21-1] 648585757 HMPREF9553_01980 hypothetical protein [Escherichia coli MS 200-1] 648532850 HMPREF9540_01467 conserved hypothetical protein [Escherichia coli MS 115-1] 648528279 HMPREF9536_02724 hypothetical protein [Escherichia coli MS 84-1] 648570808 HMPREF9535_02392 conserved hypothetical protein [Escherichia coli MS 78-1] 648583178 HMPREF9547_04386 hypothetical protein [Escherichia coli MS 175-1] 647941767 HMPREF0485_04604 yeaL [Klebsiella sp. 1_1_55]648578226 HMPREF9541_04708 conserved hypothetical protein [Escherichia coli MS 116-1] 645344919 ShiD9_010100003853 conserved inner membrane protein [Shigella sp. D9] 651552290 HMPREF9538_06054 hypothetical protein [Klebsiella sp. MS 92-3] 646244643 CSAG_01006 conserved hypothetical protein [Citrobacter sp. 30_2] 648590236 HMPREF9551_01014 conserved hypothetical protein [Escherichia coli MS 196-1] 648542647 HMPREF9543_00699 conserved hypothetical protein [Escherichia coli MS 146-1] 648557349 HMPREF9534_04988 conserved hypothetical protein [Escherichia coli MS 69-1] 645349504 E4_010100004179 conserved inner membrane protein [Escherichia sp. 4_1_40B] 647456249 CW1_1394 response regulator receiver domain protein [Bacteroides ovatus SD CC 2a] 646225070 BSCG_03588 two-component system sensor histidine kinase/response regulator [Bacteroides sp. 2_2_4] 646004545 BacD2_010100009346 two-component system sensor histidine kinase/response regulator, hybrid ('one-component system') [Bacteroides sp. D2] 647442704 CW3_1134 response regulator receiver domain protein [Bacteroides xylanisolvens SD CC 1b] 647453329 CUY_0572 response regulator receiver domain protein [Bacteroides ovatus SD CMC 3f] 648905375 HMPREF9010_04162 two-component system sensor histidine kinase/response regulator, hybrid (one-component system) [Bacteroides sp. 3_1_23] 651358611 HMPREF1017_02631 hypothetical protein [Bacteroides ovatus 3_8_47FAA] 643119573 BACDOR_00482 Uncharacterized protein conserved in bacteria [Bacteroides dorei DSM 17855] 646218672 BSAG_02040 two-component system sensor histidine kinase/response regulator [Bacteroides sp. D1] 647878135 HMPREF0102_00037 two-component system sensor histidine kinase/response regulator [Bacteroides sp. 2_1_22] 648599701 HMPREF9549_04771 conserved hypothetical protein [Escherichia coli MS 185-1] 646208752 ESAG_02468 conserved hypothetical protein [Escherichia sp. 3_2_53FAA] 648552154 HMPREF9531_05139 conserved hypothetical protein [Escherichia coli MS 45-1] 648522984 HMPREF9552_03152 conserved hypothetical protein [Escherichia coli MS 198-1] 648566267 HMPREF9530_03710 conserved hypothetical protein [Escherichia coli MS 21-1] 648558944 HMPREF9550_00991 conserved hypothetical protein [Escherichia coli MS 187-1] 648539477 HMPREF9548_02962 hypothetical protein [Escherichia coli MS 182-1] 646209587 ESAG_03285 sulfate/thiosulfate transporter subunit CysT [Escherichia sp. 3_2_53FAA] 648572039 HMPREF9535_03623 sulfate ABC transporter, permease protein CysT [Escherichia coli MS 78-1] 648600222 HMPREF9549_05292 cytochrome C biogenesis protein [Escherichia coli MS 185-1] 648546527 HMPREF9543_04581 sulfate ABC transporter, permease protein CysT [Escherichia coli MS 146-1] 643145990 PROVALCAL_01668 sulfate ABC transporter, permease protein CysT [Providencia alcalifaciens DSM 30120] 646245885 CSAG_02233 sulfate/thiosulfate transporter subunit CysT [Citrobacter sp. 30_2] 645344307 ShiD9_010100000825 sulfate/thiosulfate transporter subunit [Shigella sp. D9] 650059859 HMPREF0864_00463 sulfate ABC transporter [Enterobacteriaceae bacterium 9_2_54FAA] 648543645 HMPREF9543_01698 cytochrome C biogenesis protein [Escherichia coli MS 146-1] 648521295 HMPREF9552_01462 conserved domain protein [Escherichia coli MS 198-1] 648555205 HMPREF9534_02842 sulfate ABC transporter, permease protein CysT [Escherichia coli MS 69-1] 648578693 HMPREF9541_05175 sulfate ABC transporter, permease protein CysT [Escherichia coli MS 116-1] 648591303 HMPREF9551_02082 sulfate ABC transporter, permease protein CysT [Escherichia coli MS 196-1] 648595378 HMPREF9549_00444 sulfate ABC transporter, permease protein CysT [Escherichia coli MS 185-1] 648526848 HMPREF9536_01291 sulfate ABC transporter, permease protein CysT [Escherichia coli MS 84-1] 648567644 HMPREF9530_05088 sulfate ABC transporter, permease protein CysT [Escherichia coli MS 21-1] 647937242 HMPREF0485_00139 sulfate ABC transporter, permease CysT [Klebsiella sp. 1_1_55]648589103 HMPREF9553_05328 sulfate ABC transporter, permease protein CysT [Escherichia coli MS 200-1] 645348824 E4_010100000800 sulfate/thiosulfate transporter subunit [Escherichia sp. 4_1_40B] 651551663 HMPREF9538_05427 sulfate ABC transporter, permease protein CysT [Klebsiella sp. MS 92-3] 648536354 HMPREF9540_04974 sulfate ABC transporter, permease protein CysT [Escherichia coli MS 115-1] 648536927 HMPREF9548_00411 sulfate ABC transporter, permease protein CysT [Escherichia coli MS 182-1] 648549444 HMPREF9531_02427 sulfate ABC transporter, permease protein CysT [Escherichia coli MS 45-1] 648558895 HMPREF9550_00942 sulfate ABC transporter, permease protein CysT [Escherichia coli MS 187-1] 648581795 HMPREF9547_03002 sulfate ABC transporter, permease protein CysT [Escherichia coli MS 175-1] 647882180 HMPREF0102_04029 ABC transporter permease [Bacteroides sp. 2_1_22] 648904642 HMPREF9010_02237 ABC transporter permease [Bacteroides sp. 3_1_23] 646218952 BSAG_02315 ABC transporter permease [Bacteroides sp. D1]648894402 HMPREF0106_03941 ABC transporter permease [Bacteroides sp. D22] 647441067 CW3_3396 efflux ABC transporter, permease protein [Bacteroides xylanisolvens SD CC 1b] 646006126 BacD2_010100017240 ABC transporter permease [Bacteroides sp. D2] 651540529 HMPREF9445_01605 efflux ABC transporter, permease protein [Bacteroides clarus YIT 12056] 647454327 CUY_0145 efflux ABC transporter, permease protein [Bacteroides ovatus SD CMC 3f] 651373142 HMPREF0127_04005 hypothetical protein [Bacteroides sp. 1_1_30] 644103941 COPCOM_03663 hypothetical protein [Coprococcus comes ATCC 27758] 646231370 BSEG_03838 carbohydrate esterase family 12 protein [Bacteroides dorei 5_1_36/D4] 647437567 CUU_2038 GDSL-like protein [Bacteroides vulgatus PC510]647530872 HMPREF0219_2871 ABC superfamily ATP binding cassette transporter superfamily protein [Clostridium difficile NAP07] 644271963 ROSEINA2194_03461 hypothetical protein [Roseburia inulinivorans DSM 16841] 647888687 HMPREF0105_1086 carbohydrate esterase family 12 protein [Bacteroides sp. 3_1_33FAA] 650005282 HMPREF9011_03782 hypothetical protein [Bacteroides sp. 3_1_40A] 643122470 BACDOR_03380 Predicted xylanase/chitin deacetylase [Bacteroides dorei DSM 17855] 647940528 HMPREF0485_03374 oxaloacetate decarboxylase, beta subunit [Klebsiella sp. 1_1_55] 648882423 HMPREF9007_01172 hypothetical protein [Bacteroides sp. 1_1_14] 647510160 HMPREF0220_2248 ABC superfamily ATP binding cassette transporter superfamily protein [Clostridium difficile NAP08] 647876401 HMPREF0103_2298 conserved hypothetical protein [Bacteroides sp. 2_1_33B] 645280677 B2_010100009578 putative 2', 3'-cyclic nucleotide 2'-phosphodiesterase [Bacteroides sp. 2_1_7] 646221796 BSCG_00343 ABC transporter permease [Bacteroides sp. 2_2_4] 646288901 HMPREF0619_03414 conserved hypothetical protein [Parabacteroides sp. D13] 648909135 HMPREF9008_02106 5'-nucleotidase family protein [Bacteroides sp. 20_3] 647455213 CUY_4106 conserved hypothetical protein [Bacteroides ovatus SD CMC 3f] 648888683 HMPREF0104_02520 5'-nucleotidase family protein [Bacteroides sp. 3_1_19] 651359502 HMPREF1017_03509 hypothetical protein [Bacteroides ovatus 3_8_47FAA] 645278865 B2_010100000532 putative endonuclease/exonuclease/phosphatase family protein [Bacteroides sp. 2_1_7] 647938774 HMPREF0485_01650 transcription regulatory protein opdE [Klebsiella sp. 1_1_55] 646222275 BSCG_00818 peptidase [Bacteroides sp. 2_2_4] 650010945 HMPREF1007_03145 hypothetical protein [Bacteroides sp. 4_1_36] 644391106 HMPREF0539_0481 xre family transcriptional regulator [Lactobacillus rhamnosus LMS2-1] 650596784 CK3_12330 Uncharacterized MobA-related protein [Clostridiales sp. SS3/4] 647896910 HMPREF0969_00842 conserved hypothetical protein [Bacteroides sp. D20] 648539013 HMPREF9548_02498 cytochrome C biogenesis protein [Escherichia coli MS 182-1] 646209840 ESAG_03538 formate-dependent nitrite reductase [Escherichia sp. 3_2_53FAA] 645346635 ShiD9_010100012465 formate-dependent nitrite reductase complex subunit NrfF [Shigella sp. D9] 648529913 HMPREF9536_04360 cytochrome C biogenesis protein [Escherichia coli MS 84-1] 645351940 E4_010100016373 formate-dependent nitrite reductase complex subunit NrfF [Escherichia sp. 4_1_40B] 646266352 ESCG_00846 conserved hypothetical protein [Escherichia sp. 1_1_43] 648532193 HMPREF9540_00809 cytochrome C biogenesis protein [Escherichia coli MS 115-1] 648560726 HMPREF9550_02773 cytochrome C biogenesis protein [Escherichia coli MS 187-1] 648547681 HMPREF9531_00663 cytochrome C biogenesis protein [Escherichia coli MS 45-1] 648573260 HMPREF9535_04845 cytochrome C biogenesis protein [Escherichia coli MS 78-1] 648589640 HMPREF9551_00418 cytochrome C biogenesis protein [Escherichia coli MS 196-1] 648582054 HMPREF9547_03262 cytochrome C biogenesis protein [Escherichia coli MS 175-1] 648585326 HMPREF9553_01549 cytochrome C biogenesis protein [Escherichia coli MS 200-1] 648573823 HMPREF9541_00303 cytochrome C biogenesis protein [Escherichia coli MS 116-1] 650543885 ENC_40020 hypothetical protein [Enterobacter cloacae cloacae NCTC 9394] 650590255 ES1_16010 ATP synthase subunit C. [Eubacterium siraeum V10Sc8a]651550612 HMPREF9538_04375 transporter, small conductance mechanosensitive ion channel MscS family protein [Klebsiella sp. MS 92-3] 646898472 LRHM_2731 transcriptional regulator [Lactobacillus rhamnosus GG, ATCC 53103] 648585077 HMPREF9553_01300 Ppx/GppA phosphatase family protein [Escherichia coli MS 200-1] 648527680 HMPREF9536_02124 Ppx/GppA phosphatase family protein [Escherichia coli MS 84-1] 648567341 HMPREF9530_04785 Ppx/GppA phosphatase family protein [Escherichia coli MS 21-1] 645353128 E4_010100022326 guanosine pentaphosphate phosphohydrolase [Escherichia sp. 4_1_40B] 648560308 HMPREF9550_02355 Ppx/GppA phosphatase family protein [Escherichia coli MS 187-1] 648524543 HMPREF9552_04712 Ppx/GppA phosphatase family protein [Escherichia coli MS 198-1] 648550453 HMPREF9531_03437 Ppx/GppA phosphatase family protein [Escherichia coli MS 45-1] 648574481 HMPREF9541_00961 Ppx/GppA phosphatase family protein [Escherichia coli MS 116-1] 648554706 HMPREF9534_02343 Ppx/GppA phosphatase family protein [Escherichia coli MS 69-1] 648544703 HMPREF9543_02756 Ppx/GppA phosphatase family protein [Escherichia coli MS 146-1] 648579916 HMPREF9547_01122 Ppx/GppA phosphatase family protein [Escherichia coli MS 175-1] 648536501 HMPREF9540_05121 Ppx/GppA phosphatase family protein [Escherichia coli MS 115-1] 648596347 HMPREF9549_01414 Ppx/GppA phosphatase family protein [Escherichia coli MS 185-1] 645348414 ShiD9_010100021332 guanosine pentaphosphate phosphohydrolase [Shigella sp. D9] 646268262 ESCG_02094 guanosine-5'-triphosphate,3'-diphosphate pyrophosphatase [Escherichia sp. 1_1_43] 648594024 HMPREF9551_04804 Ppx/GppA phosphatase family protein [Escherichia coli MS 196-1] 648538001 HMPREF9548_01485 Ppx/GppA phosphatase family protein [Escherichia coli MS 182-1] 646211240 ESAG_04930 guanosine-5'-triphosphate,3'-diphosphate pyrophosphatase [Escherichia sp. 3_2_53FAA] 648568952 HMPREF9535_00535 Ppx/GppA phosphatase family protein [Escherichia coli MS 78-1] 648593289 HMPREF9551_04069 nitrite transporter [Escherichia coli MS 196-1] 648545466 HMPREF9543_03519 nitrite transporter [Escherichia coli MS 146-1] 648523666 HMPREF9552_03834 nitrite transporter [Escherichia coli MS 198-1] 648580565 HMPREF9547_01772 nitrite transporter [Escherichia coli MS 175-1] 648556756 HMPREF9534_04394 nitrite transporter [Escherichia coli MS 69-1] 645350063 E4_010100006994 nitrate/nitrite transporter [Escherichia sp. 4_1_40B] 644102766 COPCOM_02487 electron transport complex, RnfABCDGE type, D subunit [Coprococcus comes ATCC 27758] 651383456 HMPREF9477_00720 hypothetical protein [Lachnospiraceae bacterium 2_1_46FAA] 651349687 HMPREF0992_01853 hypothetical protein [Lachnospiraceae bacterium 6_1_63FAA] 651328774 HMPREF0990_00997 hypothetical protein [Lachnospiraceae bacterium 1_1_57FAA] 651330706 HMPREF0988_00134 hypothetical protein [Lachnospiraceae bacterium 1_4_56FAA] 651335340 HMPREF0991_01506 hypothetical protein [Lachnospiraceae bacterium 2_1_58FAA] 650047805 HMPREF1026_00500 Na-translocating NADH-quinone reductase [Lachnospiraceae bacterium sp. 8_1_57FAA] 651368271 HMPREF1025_02141 hypothetical protein [Lachnospiraceae bacterium 3_1_46FAA] 646208194 ESAG_01916 nitrite extrusion protein 1 [Escherichia sp. 3_2_53FAA] 648588549 HMPREF9553_04774 nitrite transporter [Escherichia coli MS 200-1] 648570380 HMPREF9535_01964 nitrite transporter [Escherichia coli MS 78-1] 648578787 HMPREF9541_05269 nitrite transporter [Escherichia coli MS 116-1] 648541116 HMPREF9548_04602 nitrite transporter [Escherichia coli MS 182-1] 648530378 HMPREF9536_04825 nitrite transporter [Escherichia coli MS 84-1] 648547244 HMPREF9531_00226 nitrite transporter [Escherichia coli MS 45-1] 648595901 HMPREF9549_00967 nitrite transporter [Escherichia coli MS 185-1] 648558056 HMPREF9550_00103 nitrite transporter [Escherichia coli MS 187-1] 648566899 HMPREF9530_04343 nitrite transporter [Escherichia coli MS 21-1] 645345425 ShiD9_010100006402 nitrate/nitrite transporter [Shigella sp. D9] 648584330 HMPREF9553_00553 hypothetical protein [Escherichia coli MS 200-1] 651334690 HMPREF0991_00859 hypothetical protein [Lachnospiraceae bacterium 2_1_58FAA] 648530292 HMPREF9536_04739 hypothetical protein [Escherichia coli MS 84-1] 643147786 PROVALCAL_03473 Response regulators consisting of a CheY-like receiver domain and a winged-helix DNA-binding domain [Providencia alcalifaciens DSM 30120] 647442144 CW3_0806 conserved hypothetical protein [Bacteroides xylanisolvens SD CC 1b] 647450958 CUY_4616 conserved hypothetical protein [Bacteroides ovatus SD CMC 3f] 648892251 HMPREF0106_01775 conserved hypothetical protein [Bacteroides sp. D22] 651369650 HMPREF0127_00550 hypothetical protein [Bacteroides sp. 1_1_30] 646223825 BSCG_02356 conserved hypothetical protein [Bacteroides sp. 2_2_4] 644180003 CLOSTASPAR_04620 Response regulators consisting of a CheY-like receiver domain and a winged-helix DNA-binding domain [Clostridium asparagiforme DSM 15981] 650188158 HMPREF9436_01896 putative KDP operon transcriptional regulatory protein KdpE [Faecalibacterium cf. prausnitzii KLE1255] 650027072 HMPREF1011_00516 response regulator receiver domain-containing protein [Anaerostipes sp. 3_2_56FAA] 650556253 FP2_19490 Response regulators consisting of a CheY-like receiver domain and a winged-helix DNA-binding domain [Faecalibacterium prausnitzii L2-6] 643184261 EUBIFOR_01499 Response regulators consisting of a CheY-like receiver domain and a winged-helix DNA-binding domain [Eubacterium biforme DSM 3989] 650559857 FPR_27460 Response regulators consisting of a CheY-like receiver domain and a winged-helix DNA-binding domain [Faecalibacterium prausnitzii SL3/3] 644158263 HOLDEFILI_00005 Response regulators consisting of a CheY-like receiver domain and a winged-helix DNA-binding domain [Holdemania filiformis VPI J1-31B-1, DSM 12042] 650562669 MHY_04970 Response regulators consisting of a CheY-like receiver domain and a winged-helix DNA-binding domain [Megamonas hypermegale ART12/1] 646241223 MBAG_01060 conserved hypothetical protein [Coprobacillus sp. D7] 643112755 CLONEX_00261 Response regulators consisting of a CheY-like receiver domain and a winged-helix DNA-binding domain [Clostridium nexile DSM 1787] 644096990 PROPEN_01698 Response regulators consisting of a CheY-like receiver domain and a winged-helix DNA-binding domain [Proteus penneri ATCC 35198] 651350965 HMPREF0987_00485 hypothetical protein [Lachnospiraceae bacterium 9_1_43BFAA] 644227085 EUBHAL_01530 electron transport complex, RnfABCDGE type, D subunit [Eubacterium hallii DSM 3353] 646108045 HMPREF0494_0359 conserved hypothetical protein [Lactobacillus antri DSM 16041] 643115410 CLONEX_02919 electron transport complex, RnfABCDGE type, D subunit [Clostridium nexile DSM 1787] 647938633 HMPREF0485_01509 hypothetical protein [Klebsiella sp. 1_1_55] 651550285 HMPREF9538_04048 fimbrial protein [Klebsiella sp. MS 92-3] 650540371 CCU_24070 Predicted integral membrane protein [Coprococcus sp. ART55/1] 648582837 HMPREF9547_04045 general secretion pathway protein L [Escherichia coli MS 175-1] 650565199 ROI_08320 Predicted hydrolase (metallo-beta-lactamase superfamily) [Roseburia intestinalis M 50/1] 647489320 HMPREF0281_00213 glutamate transport ATP-binding protein [Corynebacterium ammoniagenes DSM 20306] 651516134 HMPREF9412_2818 HD domain protein [Paenibacillus sp. HGF5] 645274522 Bfra3_010100003045 putative esterase [Bacteroides fragilis 3_1_12] 650521373 AL1_09950 hypothetical protein [Alistipes shahii WAL 8301] 648535729 HMPREF9540_04347 PRD domain protein [Escherichia coli MS 115-1] 648926749 HMPREF0326_01475 rhomboid family protein [Desulfovibrio sp. 3_1_syn3] 643148124 PROVALCAL_03811 hypothetical protein [Providencia alcalifaciens DSM 30120] 651348165 HMPREF0992_00365 hypothetical protein [Lachnospiraceae bacterium 6_1_63FAA] 644157867 RUMHYD_03541 putative efflux protein, MATE family [Blautia hydrogenotrophica DSM 10507] 647513117 HMPREF0493_1380 Na /H antiporter [Lactobacillus amylolyticus DSM 11664] 643135786 COLSTE_01150 Response regulators consisting of a CheY-like receiver domain and a winged-helix DNA-binding domain [Collinsella stercoris DSM 13279] 646040106 ChatD1_010100029034 binding-protein-dependent transport systems inner membrane component [Clostridium hathewayi DSM 13479] 648927399 HMPREF0326_02114 CDP-alcohol phosphatidyltransferase family protein [Desulfovibrio sp. 3_1_syn3] 646222494 BSCG_01035 conserved hypothetical protein [Bacteroides sp. 2_2_4] 647876593 HMPREF0103_2485 ABC transporter permease [Bacteroides sp. 2_1_33B] 646273445 BSIG_00304 conserved hypothetical protein [Bacteroides sp. 1_1_6] 650351311 HMPREF9443_01091 hypothetical protein [Phascolarctobacterium sp. YIT 12067] 650274500 HMPREF9406_1660 hypothetical protein [Clostridium sp. HGF2] 651351291 HMPREF0987_00810 hypothetical protein [Lachnospiraceae bacterium 9_1_43BFAA] 651516803 HMPREF9412_0790 pyridine nucleotide-disulfide oxidoreductase [Paenibacillus sp. HGF5] 646213523 BSBG_01832 conserved hypothetical protein [Bacteroides sp. 9_1_42FAA] 651558500 HMPREF9442_03238 hypothetical protein [Paraprevotella xylaniphila YIT 11841] 650560145 FPR_30670 conserved hypothetical protein TIGR00043 [Faecalibacterium prausnitzii SL3/3] 644182000 CLOSTASPAR_06618 CAAX amino terminal protease family. [Clostridium asparagiforme DSM 15981] 650187840 HMPREF9436_01578 conserved hypothetical protein TIGR00043 [Faecalibacterium cf. prausnitzii KLE1255] 647448781 CUW_0440 DNA-binding protein [Turicibacter sanguinis PC909] 648925517 HMPREF0326_00253 iron-sulfur cluster-binding protein [Desulfovibrio sp. 3_1_syn3]643913915 Cbac1_010100001995 diguanylate cyclase/phosphodiesterase [Clostridiales sp. 1_7_47FAA] 650521177 AL1_07600 Predicted hydrolase of the metallo-beta-lactamase superfamily [Alistipes shahii WAL 8301] 651570860 HMPREF9413_1869 putative aliphatic sulfonates transport permease protein SsuC [Paenibacillus sp. HGF7] 648564583 HMPREF9530_02026 bacterial extracellular solute-binding protein, family 5 [Escherichia coli MS 21-1] 646003609 BacD2_010100004621 putative transmembrane mobilisation protein [Bacteroides sp. D2] 651352667 HMPREF0987_02151 hypothetical protein [Lachnospiraceae bacterium 9_1_43BFAA] 650186455 HMPREF9436_00192 TraG/TraD family protein [Faecalibacterium cf. prausnitzii KLE1255] 650545835 EC1_18790 Response regulators consisting of a CheY-like receiver domain and a winged-helix DNA-binding domain [Eubacterium cylindroides T2-87] 650558585 FPR_13180 Type IV secretory pathway, VirD4 components [Faecalibacterium prausnitzii SL3/3] 647369369 EDWATA_02100 putative ABC transporter, permease protein [Edwardsiella tarda ATCC 23685] 650187466 HMPREF9436_01203 TraG/TraD family protein [Faecalibacterium cf. prausnitzii KLE1255] 647941285 HMPREF0485_04125 fimbrial morphology [Klebsiella sp. 1_1_55] 651551067 HMPREF9538_04831 ABC transporter, substrate-binding protein, family 5 [Klebsiella sp. MS 92-3] 651543799 HMPREF9446_01544 polysaccharide biosynthesis protein [Bacteroides fluxus YIT 12057] 650055436 HMPREF0177_01823 ribosomal L5P family protein [Bifidobacterium sp. 12_1_47BFAA] 650528031 BIL_04240 LSU ribosomal protein L5P [Bifidobacterium longum longum F8] 643913229 BloniC5_010100009395 50S ribosomal protein L5 [Bifidobacterium longum longum CCUG 52486] 651382993 HMPREF9477_00264 hypothetical protein [Lachnospiraceae bacterium 2_1_46FAA] 643911022 BbifN4_010100007817 50S ribosomal protein L5 [Bifidobacterium bifidum NCIMB 41171] 646252343 FSAG_01313 conserved hypothetical protein [Fusobacterium sp. 2_1_31] 646240441 MBAG_00279 two-component system transcriptional regulator [Coprobacillus sp. D7] 643914832 Cbac1_010100006573 auxin efflux carrier [Clostridiales sp. 1_7_47FAA] 647881619 HMPREF0102_03473 DNA topoisomerase I [Bacteroides sp. 2_1_22] 643114071 CLONEX_01578 hypothetical protein [Clostridium nexile DSM 1787] 645351468 E4_010100013999 putative MFS-family transport protein [Escherichia sp. 4_1_40B] 647367772 EDWATA_00503 thiamin metabolism associated protein [Edwardsiella tarda ATCC 23685] 647875464 HMPREF0103_1383 conserved hypothetical protein [Bacteroides sp. 2_1_33B] 648908282 HMPREF9008_01652 putative endonuclease/exonuclease/phosphatase family protein [Bacteroides sp. 20_3] 648887083 HMPREF0104_00922 endonuclease/exonuclease/phosphatase [Bacteroides sp. 3_1_19] 646286485 HMPREF0619_01034 conserved hypothetical protein [Parabacteroides sp. D13] 651551905 HMPREF9538_05669 hypothetical protein [Klebsiella sp. MS 92-3] 644393128 HMPREF0539_2484 CPA2 family monovalent cation:proton (H ) antiporter-2 [Lactobacillus rhamnosus LMS2-1] 651554871 HMPREF9439_02418 permease, YjgP/YjgQ family [Parasutterella excrementihominis YIT 11859] 644158927 HOLDEFILI_00670 hypothetical protein [Holdemania filiformis VPI J1-31B-1, DSM 12042] 646897627 LRHM_1901 Na /H antiporter [Lactobacillus rhamnosus GG, ATCC 53103] 648925050 HMPREF0189_02116 permease YjgP/YjgQ [Burkholderiales bacterium 1_1_47] 644328470 HMPREF0530_2293 glycine--tRNA ligase [Lactobacillus paracasei ATCC 25302] 650082280 HMPREF9475_01584 hypothetical protein [Clostridium symbiosum WAL-14673] 644355109 HMPREF0352_2149 ABC superfamily ATP binding cassette transporter, membrane protein [Enterococcus faecium TX1330] 650559696 FPR_25620 Predicted membrane protein [Faecalibacterium prausnitzii SL3/3] 650077654 HMPREF9474_01708 hypothetical protein [Clostridium symbiosum WAL-14163] 644098745 PROPEN_03458 Uncharacterized membrane-associated protein [Proteus penneri ATCC 35198] 646006165 BacD2_010100017435 hypothetical protein [Bacteroides sp. D2] 647454257 CUY_0074 PKD domain protein [Bacteroides ovatus SD CMC 3f] 651357858 HMPREF1017_01886 hypothetical protein [Bacteroides ovatus 3_8_47FAA] 651356872 HMPREF1017_00908 hypothetical protein [Bacteroides ovatus 3_8_47FAA] 643926344 Lparp8_010100001688 Glycyl-tRNA synthetase beta subunit (Glycine--tRNA ligase beta subunit) (GlyRS) [Lactobacillus paracasei 8700:2] 646007290 BacD2_010100023154 putative phage integrase [Bacteroides sp. D2] 651369250 HMPREF0127_00159 hypothetical protein [Bacteroides sp. 1_1_30] 646221716 BSCG_00263 conserved hypothetical protein [Bacteroides sp. 2_2_4] 647445068 CUO_1612 ABC transporter, permease protein [Enterococcus faecalis PC4.1] 650521882 AL1_16290 hypothetical protein [Alistipes shahii WAL 8301] 646274622 BSIG_01466 peptidyl-prolyl cis-trans isomerase [Bacteroides sp. 1_1_6] 643156423 PRABACTJOHN_02052 putative efflux protein, MATE family [Parabacteroides johnsonii DSM 18315] 646260622 OFBG_00434 AraJ protein [Oxalobacter formigenes OXCC13] 650063509 HMPREF0864_04057 hypothetical protein [Enterobacteriaceae bacterium 9_2_54FAA] 643145705 PROVALCAL_01382 Uncharacterized membrane-associated protein [Providencia alcalifaciens DSM 30120] 644327138 HMPREF0530_0979 ApbE protein [Lactobacillus paracasei ATCC 25302] 647879967 HMPREF0102_01841 conserved hypothetical protein [Bacteroides sp. 2_1_22] 646219318 BSAG_02678 conserved hypothetical protein [Bacteroides sp. D1] 646210728 ESAG_04421 conserved hypothetical protein [Escherichia sp. 3_2_53FAA] 646224746 BSCG_03264 conserved hypothetical protein [Bacteroides sp. 2_2_4] 651517449 HMPREF9412_4232 peptidase propeptide and YpeB domain protein [Paenibacillus sp. HGF5] 648894538 HMPREF0106_04079 transcriptional regulator [Bacteroides sp. D22] 648905767 HMPREF9010_03587 transcriptional regulator [Bacteroides sp. 3_1_23] 646006668 BacD2_010100020019 putative regulatory protein [Bacteroides sp. D2] 650568357 RO1_04000 hypothetical protein [Roseburia intestinalis XB6B4] 646289055 HMPREF0619_03567 conserved hypothetical protein [Parabacteroides sp. D13] 647877251 HMPREF0103_3135 conserved hypothetical protein [Bacteroides sp. 2_1_33B] 648889363 HMPREF0104_03199 conserved hypothetical protein [Bacteroides sp. 3_1_19] 648924658 HMPREF0189_01578 putative membrane protein [Burkholderiales bacterium 1_1_47] 648910841 HMPREF9008_01966 conserved hypothetical protein [Bacteroides sp. 20_3] 651557268 HMPREF9442_02006 hypothetical protein [Paraprevotella xylaniphila YIT 11841] 645282361 B2_010100018018 hypothetical protein [Bacteroides sp. 2_1_7] 651554194 HMPREF9439_01741 putative membrane protein [Parasutterella excrementihominis YIT 11859] 651516359 HMPREF9412_4202 transporter, major facilitator family protein [Paenibacillus sp. HGF5] 648553070 HMPREF9534_00707 conserved hypothetical protein [Escherichia coli MS 69-1] 648550252 HMPREF9531_03236 conserved hypothetical protein [Escherichia coli MS 45-1] 646266592 ESCG_01081 peptidase M48 [Escherichia sp. 1_1_43] 648599190 HMPREF9549_04259 conserved hypothetical protein [Escherichia coli MS 185-1] 650273052 HMPREF9406_4121 PRD domain protein [Clostridium sp. HGF2] 647367697 EDWATA_00428 zinc transporter ZupT [Edwardsiella tarda ATCC 23685] 651384306 HMPREF9477_01558 hypothetical protein [Lachnospiraceae bacterium 2_1_46FAA] HCV_G1_NS2_794 650020844 HMPREF1004_02309 peptidase M48, Ste24p [Ralstonia sp. 5_7_47FAA] 64621849 vs. human proteome vs. human microbiome Induced Treg response Example: HCV Vaccine One “special” epitope: cross-reactive 24Ep Vax - Non-Conf dent a
  24. 24. 25 DNA Vector DNA insert Intended Protein Product: Many epitopes strung together in a “String-of-Beads” Protein product (folded) Multi-Epitope Gene Design EpiVax - Non-Confidential
  25. 25. DNA – chain of epitopes, or peptide in liposomes ICS-optimized proteins in VLPICS-optimized whole proteins Multiple Delivery Platforms Possible EpiVax - Non-Confidential 26
  26. 26. Vaccine Immunogenic Epitopes Shared Immunogenic Epitopes smallpoxvaccinia Case Study: Smallpox Vaccine VennVax 27
  27. 27. Immunogenicity Day 56 1. epitope DNA vaccine prime (IM) 2. epitope peptide boost (IN) Immunizations Days 0, 14, 28, 42 Challenge Day 65 Case Study: VennVax Immunization in HLA DR3 Transgenic Mice Moise L et al. Vaccine. 2011;29:501-11 • Challenge done at 10X LD50 for Smallpox • Related publication: http://www.ncbi.nlm.nih.gov/pubmed/21055490 EpiVax - Non-Confidential 28
  28. 28. Case Study: VennVax Protection: Survival 0% 20% 40% 60% 80% 100% 0 2 4 6 8 10 12 14 16 18 Survival Days Post-Infection VennVax Placebo Moise et al. Vaccine. 2011; 29:501-11 100% protection VS Placebo EpiVax - Non-Confidential 29
  29. 29. Many other examples . . . EpiVax - Non-Confidential 30 http://www.epivax.com/publications/vaccine-publications/ 1: 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 13;10(2). [Epub ahead of print] PubMed PMID: 24525618. 2: Moise L, Tassone R, Latimer H, Terry F, Levitz L, Haran JP, Ross TM, Boyle CM, Martin WD, De Groot AS. Immunization with cross-conserved H1N1 influenza CD4+ T-cell epitopes lowers viral burden in HLA DR3 transgenic mice. Hum Vaccin Immunother. 2013 Oct;9(10):2060-8. doi: 10.4161/hv.26511. Epub 2013 Sep 17. PubMed PMID: 24045788; PubMed Central PMCID: PMC3906390. 3: 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? Hum Vaccin Immunother. 2013 Sep;9(9):1877-84. doi: 10.4161/hv.25611. Epub 2013 Jul 22. PubMed PMID: 23877094; PubMed Central PMCID: PMC3906351. 4: Moise L, Terry F, Ardito M, Tassone R, Latimer H, Boyle C, Martin WD, De Groot AS. Universal H1N1 influenza vaccine development: identification of consensus class II hemagglutinin and neuraminidase epitopes derived from strains circulating between 1980 and 2011. Hum Vaccin Immunother. 2013 Jul;9(7):1598-607.
  30. 30. PigMatrix – Protecting our Food Supply PigMatrix EpiCC Andres Gutiérrez, Bill Martin Development in progress
  31. 31. 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 academic collaborators • Leasing of full iVAX toolkit available • Antigen analysis – we’ll run your antigens against our immunogenicity analysis tools EpiVax - Non-Confidential 32
  32. 32. Accessing the Tools Contact Jason Del Pozzo: bda@epivax.com Confidential 33 PreDeFT: Fee for service in silico immunogenicity analysis. Performed on a protein by protein basis. Pricing based on length of sequence(s). Limited ISPRI Website: Limited access to EpiVax’ Interactive Protein Screening and Reengineering Interface. Available for set numbers of proteins. Unlimited ISPRI Website: Unlimited access to EpiVax’ Interactive Protein Screening and Reengineering Interface. Available in three year lease periods. Fee for Service: HLA Binding Assays, HLA Transgenic Mice, ELISpot Assays. 33EpiVax - Non-Confidential

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