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West Nile virus

Table of Contents
  1. General Information
    1. NCBI Taxonomy ID
    2. Disease
    3. Introduction
    4. Microbial Pathogenesis
    5. Host Ranges and Animal Models
    6. Host Protective Immunity
  2. Vaccine Related Pathogen Genes
    1. E protein (Protective antigen)
    2. PrM (Protective antigen)
    3. C protein (Virmugen)
  3. Vaccine Related Host Genes
    1. IgG
  4. Vaccine Information
    1. ALVAC-WNV-prM/E
    2. ALVAC-WNV-PrM/E (dogs and cats)
    3. Encephalomyelitis-Influenza-West Nile Virus Eastern & Western, Killed Virus Vaccine (USDA: 13W5.20)
    4. Encephalomyelitis-Rhinopneumonitis-Influenza-West Nile Virus Eastern & Western, Killed Virus, Killed Flavivirus Chimera Vaccine-Tetanus Toxoid (USDA: 4855.R2)
    5. Encephalomyelitis-West Nile Virus Eastern & Western & Venezuelan, Killed Virus Vaccine (USDA: 14W5.23)
    6. Encephalomyelitis-West Nile Virus Eastern & Western & Venezuelan, Killed Virus Vaccine-Tetanus Toxoid (USDA: 48W5.20)
    7. Encephalomyelitis-West Nile Virus Eastern & Western & Venezuelan, Killed Virus Vaccine-Tetanus Toxoid (USDA: 48W5.23)
    8. Encephalomyelitis-West Nile Virus Eastern & Western, Killed Virus Vaccine (USDA: 14W5.22)
    9. Encephalomyelitis-West Nile Virus Eastern & Western, Killed Virus Vaccine-Tetanus Toxoid (USDA: 48W5.21)
    10. Encephalomyelitis-West Nile Virus Eastern & Western, Killed Virus Vaccine-Tetanus Toxoid (USDA: 48W5.22)
    11. Encephalomyelitis-West Nile Virus Eastern & Western, Killed Virus, Live Canarypox Vector Vaccine (USDA: 14W7.R0)
    12. Encephalomyelitis-West Nile Virus Eastern & Western, Killed Virus, Live Canarypox Vector Vaccine-Tetanus Toxoid (USDA: 48W9.R0)
    13. PreveNile
    14. RECOMBITEKEquine WNV
    15. rMV- WNV
    16. rWN/DEN4Δ30
    17. West Nile virus C protein mutant vaccine
    18. West Nile Virus DNA Vaccine (USDA: 1995.D0)
    19. West Nile virus DNA vaccine pCBWN encoding prM and E
    20. West Nile Virus Killed Virus Vaccine (USDA: 1995.20)
    21. West Nile Virus Killed Virus Vaccine (USDA: 1995.22)
    22. West Nile Virus Live Canarypox Vector Vaccine (USDA: 1991.R0)
    23. West Nile Virus Live Flavivirus Chimera Vaccine (USDA: 1991.R1)
    24. West Nile-Innovator DNA
    25. WNV recombinant E protein vaccine (WN-80E)
  5. References
I. General Information
1. NCBI Taxonomy ID:
11082
2. Disease:
West Nile fever
3. Introduction
West Nile virus (WNV) is a virus of the family Flaviviridae. Part of the Japanese encephalitis (JE) antigenic complex of viruses, it is found in both tropical and temperate regions. It mainly infects birds, but is known to infect humans, horses, dogs, cats, bats, chipmunks, skunks, squirrels, and domestic rabbits. The main route of human infection is through the bite of an infected mosquito (Wiki: West Nile). WNV was first detected in North America in 1999 and spread rapidly across the USA and into Canada, Mexico, and Central and South America. The virus is transmitted via mosquitoes, primarily through the bite of Culex species but also by many other genera of mosquitoes. Birds are the natural hosts and serve as the zoonotic reservoir. Mammals and reptiles are considered to be incidental hosts from which further transmission generally does not occur (Lieberman et al., 2009).
4. Microbial Pathogenesis
The mechanisms by which WNV and other neurotropic flaviviruses cross the blood-brain barrier (BBB) remain largely unknown, although tumor necrosis factor alpha (TNF-α)-mediated changes in endothelial cell permeability may facilitate CNS entry. It is likely that WNV infects the CNS at least in part via hematogenous spread, as an increased viral burden in serum correlates with earlier viral entry into the brain. Additional mechanisms may contribute to WNV CNS infection, including (i) infection or passive transport through the endothelium or choroid plexus epithelial cells, (ii) infection of olfactory neurons and spread to the olfactory bulb, (iii) a “Trojan horse” mechanism in which the virus is transported by infected immune cells that traffic to the CNS, and (iv) direct axonal retrograde transport from infected peripheral neurons (Samuel and Diamond, 2006).
5. Host Ranges and Animal Models
West Nile virus mainly infects birds, but is known to infect humans, horses, dogs, cats, bats, chipmunks, skunks, squirrels, and domestic rabbits. The main route of human infection is through the bite of an infected mosquito (Wiki: West Nile).
6. Host Protective Immunity
T-cell-mediated immunity is essential for controlling WNV infection in the CNS. Both humoral and cellular immune responses are likely essential in protection from WNV infection (Samuel and Diamond, 2006).
1. C protein
  • Gene Name : C protein
  • Sequence Strain (Species/Organism) : West Nile virus
  • NCBI Protein GI : 158516889
  • Other Database IDs : CDD:144552
    VBRC:36387
  • Taxonomy ID : 11082
  • Gene Strand (Orientation) : ?
  • Protein Name : capsid protein
  • Protein Length : 105
  • Protein Note : lineage 1; Vero cell passage 2 after isolation
  • Protein Sequence : Show Sequence
    >gi|158516889|ref|YP_001527878.1| capsid protein [West Nile virus]
    MSKKPGGPGKSRAVNMLKRGMPRVLSLIGLKRAMLSLIDGKGPIRFVLALLAFFRFTAIAPTRAVLDRWR
    GVNKQTAMKHLLSFKKELGTLTSAINRRSSKQKKR
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A virus with a C protein mutation is attenuated in mice and induces significant protection from challenge with wild type West Nile virus (Schlick et al., 2010)
  • Related Vaccine(s): West Nile virus C protein mutant vaccine
2. E protein
  • Gene Name : E protein
  • VO ID : VO_0011177
  • NCBI Protein GI : 111145461
  • 3D structure: PDB ID : 2I69
  • Other Database IDs : CDD:279241
    CDD:213392
    CDD:213897
  • Taxonomy ID : 11082
  • Gene Strand (Orientation) : ?
  • Protein Name : E protein
  • Protein pI : 7.52
  • Protein Weight : 49765.38
  • Protein Length : 559
  • Protein Note : Flavivirus glycoprotein, central and dimerization domains; pfam00869
  • Protein Sequence : Show Sequence
    >ABH06950.1 E protein, partial [West Nile virus]
    FNCLGMSNRDFLEGVSGATWVDLVLEGDSCVTIMSKDKPTIDVKMMNMEAANLAEVRSYCYLATVSDLST
    KAACPTMGEAHNDKRADPAFVCRQGVVDRGWGNGCGLFGKGSIDTCAKFACSTKAIGRTILKENIKYEVA
    IFVHGPTTVESHGNYSTQAGATQAGRFSITPAAPSYTLKLGEYGEVTVDCEPRSGIDTNAYYVMTVGTKT
    FLVHREWFMDLNLPWSSAGSTVWRNRETLMEFEEPHATKQSVIALGSQEGALHQALAGAIPVEFSSNTVK
    LTSGHLKCRVKMEKLQLKGTTYGVCSKAFKFLGTPADTGHGTVVLELQYTGTDGPCKVPISSVASLNDLT
    PVGRLVTVNPFVSVATANAKVLIELEPPFGDSYIVVGRGEQQINHHWHKSGSSIGKAFTTTLKGAQRLAA
    LGDTAWDFGSVGGVFTSVGKAVHQVFGGAFRSLFGGMSWITQGLLGALLLWMGINARDRSIALTFLAVGG
    VLLFLSVNVHA
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : The immunogenicity and protective efficacy of a recombinant subunit West Nile virus (WNV) vaccine was evaluated in rhesus macaques (Macaca mulatta). The vaccine consisted of a recombinant envelope (E) protein truncated at the C-terminal end, resulting in a polypeptide containing 80% of the N-terminal amino acids of the native WNV protein (WN-80E), mixed with an adjuvant (GPI-0100). Groups of monkeys were immunized with the WN-80E/GPI-0100 vaccine or an adjuvant-only control formulation. Animals were then challenged by inoculation of wild-type WNV, and the level of viremia in each animal was monitored daily for 10 days. The results showed that whereas all animals in the control group had detectable viremia for at least 3 days after challenge, all of the vaccinated animals were negative on all days after challenge. Thus, the WN-80E vaccine was 100% efficacious in protecting monkeys against infection with WNV (Lieberman et al., 2009).
  • Related Vaccine(s): ALVAC-WNV-PrM/E (dogs and cats) , West Nile virus DNA vaccine pCBWN encoding prM and E
3. PrM
  • Gene Name : PrM
  • Sequence Strain (Species/Organism) : West Nile virus
  • VO ID : VO_0011179
  • NCBI Gene ID : 5714902
  • NCBI Protein GI : 158516888
  • Locus Tag : WNVNY99_gp1
  • Genbank Accession : DQ211652
  • Protein Accession : YP_001527877
  • Taxonomy ID : 11082
  • Gene Starting Position : 96
  • Gene Ending Position : 10397
  • Gene Strand (Orientation) : +
  • Protein Name : mRNA
  • Protein pI : 8.52
  • Protein Weight : 353459.58
  • Protein Length : 3433
  • DNA Sequence : Show Sequence
    >NC_009942.1:96-10397 West Nile virus lineage 1, complete genome
    GATGTCTAAGAAACCAGGAGGGCCCGGCAAGAGCCGGGCTGTCAATATGCTAAAACGCGGAATGCCCCGC
    GTGTTGTCCTTGATTGGACTGAAGAGGGCTATGTTGAGCCTGATCGACGGCAAGGGGCCAATACGATTTG
    TGTTGGCTCTCTTGGCGTTCTTCAGGTTCACAGCAATTGCTCCGACCCGAGCAGTGCTGGATCGATGGAG
    AGGTGTGAACAAACAAACAGCGATGAAACACCTTCTGAGTTTTAAGAAGGAACTAGGGACCTTGACCAGT
    GCTATCAATCGGCGGAGCTCAAAACAAAAGAAAAGAGGAGGAAAGACCGGAATTGCAGTCATGATTGGCC
    TGATCGCCAGCGTAGGAGCAGTTACCCTCTCTAACTTCCAAGGGAAGGTGATGATGACGGTAAATGCTAC
    TGACGTCACAGATGTCATCACGATTCCAACAGCTGCTGGAAAGAACCTATGCATTGTCAGAGCAATGGAT
    GTGGGATACATGTGCGATGATACTATCACTTATGAATGCCCAGTACTGTCGGCTGGTAATGATCCAGAAG
    ACATCGACTGTTGGTGCACAAAGTCAGCAGTCTACGTCAGGTATGGAAGATGCACCAAGACACGCCACTC
    AAGACGCAGTCGGAGGTCACTGACAGTGCAGACACACGGAGAAAGCACTCTAGCGAACAAGAAGGGGGCT
    TGGATGGACAGCACCAAGGCCACAAGGTATTTGGTAAAAACAGAATCATGGATCTTGAGGAACCCTGGAT
    ATGCCCTGGTGGCAGCCGTCATTGGTTGGATGCTTGGGAGCAACACCATGCAGAGAGTTGTGTTTGTCGT
    GCTATTGCTTTTGGTGGCCCCAGCTTACAGCTTCAACTGCCTTGGAATGAGCAACAGAGACTTCTTGGAA
    GGAGTGTCTGGAGCAACATGGGTGGATTTGGTTCTCGAAGGCGACAGCTGCGTGACTATCATGTCTAAGG
    ACAAGCCTACCATCGATGTGAAGATGATGAATATGGAGGCGGCCAACCTGGCAGAGGTCCGCAGTTATTG
    CTATTTGGCTACCGTCAGCGATCTCTCCACCAAAGCTGCGTGCCCGACCATGGGAGAAGCTCACAATGAC
    AAACGTGCTGACCCAGCTTTTGTGTGCAGACAAGGAGTGGTGGACAGGGGCTGGGGCAACGGCTGCGGAC
    TATTTGGCAAAGGAAGCATTGACACATGCGCCAAATTTGCCTGCTCTACCAAGGCAATAGGAAGAACCAT
    CTTGAAAGAGAATATCAAGTACGAAGTGGCCATTTTTGTCCATGGACCAACTACTGTGGAGTCGCACGGA
    AACTACTCCACACAGGTTGGAGCCACTCAGGCAGGGAGACTCAGCATCACTCCTGCGGCGCCTTCATACA
    CACTAAAGCTTGGAGAATATGGAGAGGTGACAGTGGACTGTGAACCACGGTCAGGGATTGACACCAATGC
    ATACTACGTGATGACTGTTGGAACAAAGACGTTCTTGGTCCATCGTGAGTGGTTCATGGACCTCAACCTC
    CCTTGGAGCAGTGCTGGAAGTACTGTGTGGAGGAACAGAGAGACGTTAATGGAGTTTGAGGAACCACACG
    CCACGAAGCAGTCTGTGATAGCATTGGGCTCACAAGAGGGAGCTCTGCATCAAGCTTTGGCTGGAGCCAT
    TCCTGTGGAATTTTCAAGCAACACTGTCAAGTTGACGTCGGGTCATTTGAAGTGTAGAGTGAAGATGGAA
    AAATTGCAGTTGAAGGGAACAACCTATGGCGTCTGTTCAAAGGCTTTCAAGTTTCTTGGGACTCCCGCAG
    ACACAGGTCACGGCACTGTGGTGTTGGAATTGCAGTACACTGGCACGGATGGACCTTGCAAAGTTCCTAT
    CTCGTCAGTGGCTTCATTGAACGACCTAACGCCAGTGGGCAGATTGGTCACTGTCAACCCTTTTGTTTCA
    GTGGCCACGGCCAACGCTAAGGTCCTGATTGAATTGGAACCACCCTTTGGAGACTCATACATAGTGGTGG
    GCAGAGGAGAACAACAGATCAATCACCATTGGCACAAGTCTGGAAGCAGCATTGGCAAAGCCTTTACAAC
    CACCCTCAAAGGAGCGCAGAGACTAGCCGCTCTAGGAGACACAGCTTGGGACTTTGGATCAGTTGGAGGG
    GTGTTCACCTCAGTTGGGAAGGCTGTCCATCAAGTGTTCGGAGGAGCATTCCGCTCACTGTTCGGAGGCA
    TGTCCTGGATAACGCAAGGATTGCTGGGGGCTCTCCTGTTGTGGATGGGCATCAATGCTCGTGATAGGTC
    CATAGCTCTCACGTTTCTCGCAGTTGGAGGAGTTCTGCTCTTCCTCTCCGTGAACGTGCACGCTGACACT
    GGGTGTGCCATAGACATCAGCCGGCAAGAGCTGAGATGTGGAAGTGGAGTGTTCATACACAATGATGTGG
    AGGCTTGGATGGACCGGTACAAGTATTACCCTGAAACGCCACAAGGCCTAGCCAAGATCATTCAGAAAGC
    TCATAAGGAAGGAGTGTGCGGTCTACGATCAGTTTCCAGACTGGAGCATCAAATGTGGGAAGCAGTGAAG
    GACGAGCTGAACACTCTTTTGAAGGAGAATGGTGTGGACCTTAGTGTCGTGGTTGAGAAACAGGAGGGAA
    TGTACAAGTCAGCACCTAAACGCCTCACCGCCACCACGGAAAAATTGGAAATTGGCTGGAAGGCCTGGGG
    AAAGAGTATTTTATTTGCACCAGAACTCGCCAACAACACCTTTGTGGTTGATGGTCCGGAGACCAAGGAA
    TGTCCGACTCAGAATCGCGCTTGGAATAGCTTAGAAGTGGAGGATTTTGGATTTGGTCTCACCAGCACTC
    GGATGTTCCTGAAGGTCAGAGAGAGCAACACAACTGAATGTGACTCGAAGATCATTGGAACGGCTGTCAA
    GAACAACTTGGCGATCCACAGTGACCTGTCCTATTGGATTGAAAGCAGGCTCAATGATACGTGGAAGCTT
    GAAAGGGCAGTTCTGGGTGAAGTCAAATCATGTACGTGGCCTGAGACGCATACCTTGTGGGGCGATGGAA
    TCCTTGAGAGTGACTTGATAATACCAGTCACACTGGCGGGACCACGAAGCAATCACAATCGGAGACCTGG
    GTACAAGACACAAAACCAGGGCCCATGGGACGAAGGCCGGGTAGAGATTGACTTCGATTACTGCCCAGGA
    ACTACGGTCACCCTGAGTGAGAGCTGCGGACACCGTGGACCTGCCACTCGCACCACCACAGAGAGCGGAA
    AGTTGATAACAGATTGGTGCTGCAGGAGCTGCACCTTACCACCACTGCGCTACCAAACTGACAGCGGCTG
    TTGGTATGGTATGGAGATCAGACCACAGAGACATGATGAAAAGACCCTCGTGCAGTCACAAGTGAATGCT
    TATAATGCTGATATGATTGACCCTTTTCAGTTGGGCCTTCTGGTCGTGTTCTTGGCCACCCAGGAGGTCC
    TTCGCAAGAGGTGGACAGCCAAGATCAGCATGCCAGCTATACTGATTGCTCTGCTAGTCCTGGTGTTTGG
    GGGCATTACTTACACTGATGTGTTACGCTATGTCATCTTGGTGGGGGCAGCTTTCGCAGAATCTAATTCG
    GGAGGAGACGTGGTACACTTGGCGCTCATGGCGACCTTCAAGATACAACCAGTGTTTATGGTGGCATCGT
    TTCTCAAAGCGAGATGGACCAACCAGGAGAACATTTTGTTGATGTTGGCGGCTGTTTTCTTTCAAATGGC
    TTATCACGATGCCCGCCAAATTCTGCTCTGGGAGATCCCTGATGTGTTGAATTCACTGGCGGTAGCTTGG
    ATGATACTGAGAGCCATAACATTCACAACGACATCAAACGTGGTTGTTCCGCTGCTAGCCCTGCTAACAC
    CCGGGCTGAGATGCTTGAATCTGGATGTGTACAGGATACTGCTGTTGATGGTCGGAATAGGCAGCTTGAT
    CAGGGAGAAGAGGAGTGCAGCCGCAAAAAAGAAAGGAGCAAGTCTGCTATGCTTGGCTCTAGCCTCAACA
    GGACTTTTCAACCCCATGATCCTTGCTGCTGGACTGATTGCATGTGATCCCAACCGTAAACGCGGATGGC
    CCGCAACTGAAGTGATGACAGCTGTCGGCCTAATGTTTGCCATCGTCGGAGGGCTGGCAGAGCTTGACAT
    TGACTCCATGGCCATTCCAATGACTATCGCGGGGCTCATGTTTGCTGCTTTCGTGATTTCTGGGAAATCA
    ACAGATATGTGGATTGAGAGAACGGCGGACATTTCCTGGGAAAGTGATGCAGAAATTACAGGCTCGAGCG
    AAAGAGTTGATGTGCGGCTTGATGATGATGGAAACTTCCAGCTCATGAATGATCCAGGAGCACCTTGGAA
    GATATGGATGCTCAGAATGGTCTGTCTCGCGATTAGTGCGTACACCCCCTGGGCAATCTTGCCCTCAGTA
    GTTGGATTTTGGATAACTCTCCAATACACAAAGAGAGGAGGCGTGTTGTGGGACACTCCCTCACCAAAGG
    AGTACAAAAAGGGGGACACGACCACCGGCGTCTACAGGATCATGACTCGTGGGCTGCTCGGCAGTTATCA
    AGCAGGAGCGGGCGTGATGGTTGAAGGTGTTTTCCACACCCTTTGGCATACAACAAAAGGAGCCGCTTTG
    ATGAGCGGAGAGGGCCGCCTGGACCCATACTGGGGCAGTGTCAAGGAGGATCGACTTTGTTACGGAGGAC
    CCTGGAAATTGCAGCACAAGTGGAACGGGCAGGATGAGGTGCAGATGATTGTGGTGGAACCTGGCAAGAA
    CGTTAAGAACGTCCAGACGAAACCAGGGGTGTTCAAAACACCTGAAGGAGAAATCGGGGCCGTGACTTTG
    GACTTCCCCACTGGAACATCAGGCTCACCAATAGTGGACAAAAACGGTGATGTGATTGGGCTTTATGGCA
    ATGGAGTCATAATGCCCAACGGCTCATACATAAGCGCGATAGTGCAGGGTGAAAGGATGGATGAGCCAAT
    CCCAGCCGGATTCGAACCTGAGATGCTGAGGAAAAAACAGATCACTGTACTGGATCTCCATCCCGGCGCC
    GGTAAAACAAGGAGGATTCTGCCACAGATCATCAAAGAGGCCATAAACAGAAGACTGAGAACAGCCGTGC
    TAGCGCCAACCAGGGTTGTGGCTGCTGAGATGGCTGAAGCACTGAGAGGACTGCCCATCCGGTACCAGAC
    ATCCGCAGTGCCCAGAGAACATAATGGAAATGAGATTGTTGATGTCATGTGTCATGCTACCCTCACCCAC
    AGGCTGATGTCTCCTCACAGGGTGCCGAACTACAACCTGTTCGTGATGGATGAGGCTCATTTCACCGACC
    CAGCTAGCATTGCAGCAAGAGGTTACATTTCCACAAAGGTCGAGCTAGGGGAGGCGGCGGCAATATTCAT
    GACAGCCACCCCACCAGGCACTTCAGATCCATTCCCAGAGTCCAATTCACCAATTTCCGACTTACAGACT
    GAGATCCCGGATCGAGCTTGGAACTCTGGATACGAATGGATCACAGAATACACCGGGAAGACGGTTTGGT
    TTGTGCCTAGTGTCAAGATGGGGAATGAGATTGCCCTTTGCCTACAACGTGCTGGAAAGAAAGTAGTCCA
    ATTGAACAGAAAGTCGTACGAGACGGAGTACCCAAAATGTAAGAACGATGATTGGGACTTTGTTATCACA
    ACAGACATATCTGAAATGGGGGCTAACTTCAAGGCGAGCAGGGTGATTGACAGCCGGAAGAGTGTGAAAC
    CAACCATCATAACAGAAGGAGAAGGGAGAGTGATCCTGGGAGAACCATCTGCAGTGACAGCAGCTAGTGC
    CGCCCAGAGACGTGGACGTATCGGTAGAAATCCGTCGCAAGTTGGTGATGAGTACTGTTATGGGGGGCAC
    ACGAATGAAGACGACTCGAACTTCGCCCATTGGACTGAGGCACGAATCATGCTGGACAACATCAACATGC
    CAAACGGACTGATCGCTCAATTCTACCAACCAGAGCGTGAGAAGGTATATACCATGGATGGGGAATACCG
    GCTCAGAGGAGAAGAGAGAAAAAACTTTCTGGAACTGTTGAGGACTGCAGATCTGCCAGTTTGGCTGGCT
    TACAAGGTTGCAGCGGCTGGAGTGTCATACCACGACCGGAGGTGGTGCTTTGATGGTCCTAGGACAAACA
    CAATTTTAGAAGACAACAACGAAGTGGAAGTCATCACGAAGCTTGGTGAAAGGAAGATTCTGAGGCCGCG
    CTGGATTGATGCCAGGGTGTACTCGGATCACCAGGCACTAAAGGCGTTCAAGGACTTCGCCTCGGGAAAA
    CGTTCTCAGATAGGGCTCATTGAGGTTCTGGGAAAGATGCCTGAGCACTTCATGGGGAAGACATGGGAAG
    CACTTGACACCATGTACGTTGTGGCCACTGCAGAGAAAGGAGGAAGAGCTCACAGAATGGCCCTGGAGGA
    ACTGCCAGATGCTCTTCAGACAATTGCCTTGATTGCCTTATTGAGTGTGATGACCATGGGAGTATTCTTC
    CTCCTCATGCAGCGGAAGGGCATTGGAAAGATAGGTTTGGGAGGCGCTGTCTTGGGAGTCGCGACCTTTT
    TCTGTTGGATGGCTGAAGTTCCAGGAACGAAGATCGCCGGAATGTTGCTGCTCTCCCTTCTCTTGATGAT
    TGTGCTAATTCCTGAGCCAGAGAAGCAACGTTCGCAGACAGACAACCAGCTAGCCGTGTTCCTGATTTGT
    GTCATGACCCTTGTGAGCGCAGTGGCAGCCAACGAGATGGGTTGGCTAGATAAGACCAAGAGTGACATAA
    GCAGTTTGTTTGGGCAAAGAATTGAGGTCAAGGAGAATTTCAGCATGGGAGAGTTTCTTCTGGACTTGAG
    GCCGGCAACAGCCTGGTCACTGTACGCTGTGACAACAGCGGTCCTCACTCCACTGCTAAAGCATTTGATC
    ACGTCAGATTACATCAACACCTCATTGACCTCAATAAACGTTCAGGCAAGTGCACTATTCACACTCGCGC
    GAGGCTTCCCCTTCGTCGATGTTGGAGTGTCGGCTCTCCTGCTAGCAGCCGGATGCTGGGGACAAGTCAC
    CCTCACCGTTACGGTAACAGCGGCAACACTCCTTTTTTGCCACTATGCCTACATGGTTCCCGGTTGGCAA
    GCTGAGGCAATGCGCTCAGCCCAGCGGCGGACAGCGGCCGGAATCATGAAGAACGCTGTAGTGGATGGCA
    TCGTGGCCACGGACGTCCCAGAATTAGAGCGCACCACACCCATCATGCAGAAGAAAGTTGGACAGATCAT
    GCTGATCTTGGTGTCTCTAGCTGCAGTAGTAGTGAACCCGTCTGTGAAGACAGTACGAGAAGCCGGAATT
    TTGATCACGGCCGCAGCGGTGACGCTTTGGGAGAATGGAGCAAGCTCTGTTTGGAACGCAACAACTGCCA
    TCGGACTCTGCCACATCATGCGTGGGGGTTGGTTGTCATGTCTATCCATAACATGGACACTCATAAAGAA
    CATGGAAAAACCAGGACTAAAAAGAGGTGGGGCAAAAGGACGCACCTTGGGAGAGGTTTGGAAAGAAAGA
    CTCAACCAGATGACAAAAGAAGAGTTCACTAGGTACCGCAAAGAGGCCATCATCGAAGTCGATCGCTCAG
    CGGCAAAACACGCCAGGAAAGAAGGCAATGTCACTGGAGGGCATCCAGTCTCTAGGGGCACAGCAAAACT
    GAGATGGCTGGTCGAACGGAGGTTTCTCGAACCGGTCGGAAAAGTGATTGACCTTGGATGTGGAAGAGGC
    GGTTGGTGTTACTATATGGCAACCCAAAAAAGAGTCCAAGAAGTCAGAGGGTACACAAAGGGCGGTCCCG
    GACATGAAGAGCCCCAACTAGTGCAAAGTTATGGATGGAACATTGTCACCATGAAGAGTGGAGTGGATGT
    GTTCTACAGACCTTCTGAGTGTTGTGACACCCTCCTTTGTGACATCGGAGAGTCCTCGTCAAGTGCTGAG
    GTTGAAGAGCATAGGACGATTCGGGTCCTTGAAATGGTTGAGGACTGGCTGCACCGAGGGCCAAGGGAAT
    TTTGCGTGAAGGTGCTCTGTCCCTACATGCCGAAAGTCATAGAGAAGATGGAGCTGCTCCAACGCCGGTA
    TGGGGGGGGACTGGTCAGAAACCCACTCTCACGGAATTCCACGCACGAGATGTATTGGGTGAGTCGAGCT
    TCAGGCAATGTGGTACATTCAGTGAATATGACCAGCCAGGTGCTCCTAGGAAGAATGGAAAAAAGGACCT
    GGAAGGGACCCCAATACGAGGAAGATGTAAACTTGGGAAGTGGAACCAGGGCGGTGGGAAAACCCCTGCT
    CAACTCAGACACCAGTAAAATCAAGAACAGGATTGAACGACTCAGGCGTGAGTACAGTTCGACGTGGCAC
    CACGATGAGAACCACCCATATAGAACCTGGAACTATCACGGCAGTTATGATGTGAAGCCCACAGGCTCCG
    CCAGTTCGCTGGTCAATGGAGTGGTCAGGCTCCTCTCAAAACCATGGGACACCATCACGAATGTTACCAC
    CATGGCCATGACTGACACTACTCCCTTCGGGCAGCAGCGAGTGTTCAAAGAGAAGGTGGACACGAAAGCT
    CCTGAACCGCCAGAAGGAGTGAAGTACGTGCTCAACGAGACCACCAACTGGTTGTGGGCGTTTTTGGCCA
    GAGAAAAACGTCCCAGAATGTGCTCTCGAGAGGAATTCATAAGAAAGGTCAACAGCAATGCAGCTTTGGG
    TGCCATGTTTGAAGAGCAGAATCAATGGAGGAGCGCCAGAGAAGCAGTTGAAGATCCAAAATTTTGGGAG
    ATGGTGGATGAGGAGCGCGAGGCACATCTGCGGGGGGAATGTCACACTTGCATTTACAACATGATGGGAA
    AGAGAGAGAAAAAACCCGGAGAGTTCGGAAAGGCCAAGGGAAGCAGAGCCATTTGGTTCATGTGGCTCGG
    AGCTCGCTTTCTGGAGTTCGAGGCTCTGGGTTTTCTCAATGAAGACCACTGGCTTGGAAGAAAGAACTCA
    GGAGGAGGTGTCGAGGGCTTGGGCCTCCAAAAACTGGGTTACATCCTGCGTGAAGTTGGCACCCGGCCTG
    GGGGCAAGATCTATGCTGATGACACAGCTGGCTGGGACACCCGCATCACGAGAGCTGACTTGGAAAATGA
    AGCTAAGGTGCTTGAGCTGCTTGATGGGGAACATCGGCGTCTTGCCAGGGCCATCATTGAGCTCACCTAT
    CGTCACAAAGTTGTGAAAGTGATGCGCCCGGCTGCTGATGGAAGAACCGTCATGGATGTTATCTCCAGAG
    AAGATCAGAGGGGGAGTGGACAAGTTGTCACCTACGCCCTAAACACTTTCACCAACCTGGCCGTCCAGCT
    GGTGAGGATGATGGAAGGGGAAGGAGTGATTGGCCCAGATGATGTGGAGAAACTCACAAAAGGGAAAGGA
    CCCAAAGTCAGGACCTGGCTGTTTGAGAATGGGGAAGAAAGACTCAGCCGCATGGCTGTCAGTGGAGATG
    ACTGTGTGGTAAAGCCCCTGGACGATCGCTTTGCCACCTCGCTCCACTTCCTCAATGCTATGTCAAAGGT
    TCGCAAAGACATCCAAGAGTGGAAACCGTCAACTGGATGGTATGATTGGCAGCAGGTTCCATTTTGCTCA
    AACCATTTCACTGAATTGATCATGAAAGATGGAAGAACACTGGTGGTTCCATGCCGAGGACAGGATGAAT
    TGGTAGGCAGAGCTCGCATATCTCCAGGGGCCGGATGGAACGTCCGCGACACTGCTTGTCTGGCTAAGTC
    TTATGCCCAGATGTGGCTGCTTCTGTACTTCCACAGAAGAGACCTGCGGCTCATGGCCAACGCCATTTGC
    TCCGCTGTCCCTGTGAATTGGGTCCCTACCGGAAGAACCACGTGGTCCATCCATGCAGGAGGAGAGTGGA
    TGACAACAGAGGACATGTTGGAGGTCTGGAACCGTGTTTGGATAGAGGAGAATGAATGGATGGAAGACAA
    AACCCCAGTGGAGAAATGGAGTGACGTCCCATATTCAGGAAAACGAGAGGACATCTGGTGTGGCAGCCTG
    ATTGGCACAAGAGCCCGAGCCACGTGGGCAGAAAACATCCAGGTGGCTATCAACCAAGTCAGAGCAATCA
    TCGGAGATGAGAAGTATGTGGACTACATGAGTTCACTAAAGAGATATGAAGACACAACTTTGGTTGAGGA
    CACAGTACTGTA
    
    
  • Protein Sequence : Show Sequence
    >YP_001527877.1 flavivirus polyprotein [West Nile virus]
    MSKKPGGPGKSRAVNMLKRGMPRVLSLIGLKRAMLSLIDGKGPIRFVLALLAFFRFTAIAPTRAVLDRWR
    GVNKQTAMKHLLSFKKELGTLTSAINRRSSKQKKRGGKTGIAVMIGLIASVGAVTLSNFQGKVMMTVNAT
    DVTDVITIPTAAGKNLCIVRAMDVGYMCDDTITYECPVLSAGNDPEDIDCWCTKSAVYVRYGRCTKTRHS
    RRSRRSLTVQTHGESTLANKKGAWMDSTKATRYLVKTESWILRNPGYALVAAVIGWMLGSNTMQRVVFVV
    LLLLVAPAYSFNCLGMSNRDFLEGVSGATWVDLVLEGDSCVTIMSKDKPTIDVKMMNMEAANLAEVRSYC
    YLATVSDLSTKAACPTMGEAHNDKRADPAFVCRQGVVDRGWGNGCGLFGKGSIDTCAKFACSTKAIGRTI
    LKENIKYEVAIFVHGPTTVESHGNYSTQVGATQAGRLSITPAAPSYTLKLGEYGEVTVDCEPRSGIDTNA
    YYVMTVGTKTFLVHREWFMDLNLPWSSAGSTVWRNRETLMEFEEPHATKQSVIALGSQEGALHQALAGAI
    PVEFSSNTVKLTSGHLKCRVKMEKLQLKGTTYGVCSKAFKFLGTPADTGHGTVVLELQYTGTDGPCKVPI
    SSVASLNDLTPVGRLVTVNPFVSVATANAKVLIELEPPFGDSYIVVGRGEQQINHHWHKSGSSIGKAFTT
    TLKGAQRLAALGDTAWDFGSVGGVFTSVGKAVHQVFGGAFRSLFGGMSWITQGLLGALLLWMGINARDRS
    IALTFLAVGGVLLFLSVNVHADTGCAIDISRQELRCGSGVFIHNDVEAWMDRYKYYPETPQGLAKIIQKA
    HKEGVCGLRSVSRLEHQMWEAVKDELNTLLKENGVDLSVVVEKQEGMYKSAPKRLTATTEKLEIGWKAWG
    KSILFAPELANNTFVVDGPETKECPTQNRAWNSLEVEDFGFGLTSTRMFLKVRESNTTECDSKIIGTAVK
    NNLAIHSDLSYWIESRLNDTWKLERAVLGEVKSCTWPETHTLWGDGILESDLIIPVTLAGPRSNHNRRPG
    YKTQNQGPWDEGRVEIDFDYCPGTTVTLSESCGHRGPATRTTTESGKLITDWCCRSCTLPPLRYQTDSGC
    WYGMEIRPQRHDEKTLVQSQVNAYNADMIDPFQLGLLVVFLATQEVLRKRWTAKISMPAILIALLVLVFG
    GITYTDVLRYVILVGAAFAESNSGGDVVHLALMATFKIQPVFMVASFLKARWTNQENILLMLAAVFFQMA
    YHDARQILLWEIPDVLNSLAVAWMILRAITFTTTSNVVVPLLALLTPGLRCLNLDVYRILLLMVGIGSLI
    REKRSAAAKKKGASLLCLALASTGLFNPMILAAGLIACDPNRKRGWPATEVMTAVGLMFAIVGGLAELDI
    DSMAIPMTIAGLMFAAFVISGKSTDMWIERTADISWESDAEITGSSERVDVRLDDDGNFQLMNDPGAPWK
    IWMLRMVCLAISAYTPWAILPSVVGFWITLQYTKRGGVLWDTPSPKEYKKGDTTTGVYRIMTRGLLGSYQ
    AGAGVMVEGVFHTLWHTTKGAALMSGEGRLDPYWGSVKEDRLCYGGPWKLQHKWNGQDEVQMIVVEPGKN
    VKNVQTKPGVFKTPEGEIGAVTLDFPTGTSGSPIVDKNGDVIGLYGNGVIMPNGSYISAIVQGERMDEPI
    PAGFEPEMLRKKQITVLDLHPGAGKTRRILPQIIKEAINRRLRTAVLAPTRVVAAEMAEALRGLPIRYQT
    SAVPREHNGNEIVDVMCHATLTHRLMSPHRVPNYNLFVMDEAHFTDPASIAARGYISTKVELGEAAAIFM
    TATPPGTSDPFPESNSPISDLQTEIPDRAWNSGYEWITEYTGKTVWFVPSVKMGNEIALCLQRAGKKVVQ
    LNRKSYETEYPKCKNDDWDFVITTDISEMGANFKASRVIDSRKSVKPTIITEGEGRVILGEPSAVTAASA
    AQRRGRIGRNPSQVGDEYCYGGHTNEDDSNFAHWTEARIMLDNINMPNGLIAQFYQPEREKVYTMDGEYR
    LRGEERKNFLELLRTADLPVWLAYKVAAAGVSYHDRRWCFDGPRTNTILEDNNEVEVITKLGERKILRPR
    WIDARVYSDHQALKAFKDFASGKRSQIGLIEVLGKMPEHFMGKTWEALDTMYVVATAEKGGRAHRMALEE
    LPDALQTIALIALLSVMTMGVFFLLMQRKGIGKIGLGGAVLGVATFFCWMAEVPGTKIAGMLLLSLLLMI
    VLIPEPEKQRSQTDNQLAVFLICVMTLVSAVAANEMGWLDKTKSDISSLFGQRIEVKENFSMGEFLLDLR
    PATAWSLYAVTTAVLTPLLKHLITSDYINTSLTSINVQASALFTLARGFPFVDVGVSALLLAAGCWGQVT
    LTVTVTAATLLFCHYAYMVPGWQAEAMRSAQRRTAAGIMKNAVVDGIVATDVPELERTTPIMQKKVGQIM
    LILVSLAAVVVNPSVKTVREAGILITAAAVTLWENGASSVWNATTAIGLCHIMRGGWLSCLSITWTLIKN
    MEKPGLKRGGAKGRTLGEVWKERLNQMTKEEFTRYRKEAIIEVDRSAAKHARKEGNVTGGHPVSRGTAKL
    RWLVERRFLEPVGKVIDLGCGRGGWCYYMATQKRVQEVRGYTKGGPGHEEPQLVQSYGWNIVTMKSGVDV
    FYRPSECCDTLLCDIGESSSSAEVEEHRTIRVLEMVEDWLHRGPREFCVKVLCPYMPKVIEKMELLQRRY
    GGGLVRNPLSRNSTHEMYWVSRASGNVVHSVNMTSQVLLGRMEKRTWKGPQYEEDVNLGSGTRAVGKPLL
    NSDTSKIKNRIERLRREYSSTWHHDENHPYRTWNYHGSYDVKPTGSASSLVNGVVRLLSKPWDTITNVTT
    MAMTDTTPFGQQRVFKEKVDTKAPEPPEGVKYVLNETTNWLWAFLAREKRPRMCSREEFIRKVNSNAALG
    AMFEEQNQWRSAREAVEDPKFWEMVDEEREAHLRGECHTCIYNMMGKREKKPGEFGKAKGSRAIWFMWLG
    ARFLEFEALGFLNEDHWLGRKNSGGGVEGLGLQKLGYILREVGTRPGGKIYADDTAGWDTRITRADLENE
    AKVLELLDGEHRRLARAIIELTYRHKVVKVMRPAADGRTVMDVISREDQRGSGQVVTYALNTFTNLAVQL
    VRMMEGEGVIGPDDVEKLTKGKGPKVRTWLFENGEERLSRMAVSGDDCVVKPLDDRFATSLHFLNAMSKV
    RKDIQEWKPSTGWYDWQQVPFCSNHFTELIMKDGRTLVVPCRGQDELVGRARISPGAGWNVRDTACLAKS
    YAQMWLLLYFHRRDLRLMANAICSAVPVNWVPTGRTTWSIHAGGEWMTTEDMLEVWNRVWIEENEWMEDK
    TPVEKWSDVPYSGKREDIWCGSLIGTRARATWAENIQVAINQVRAIIGDEKYVDYMSSLKRYEDTTLVED
    TVL
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Starting with a previously designed eukaryotic expression vector, a recombinant plasmid (pCBWN) that expressed the WN virus prM and E proteins was constructed. A single intramuscular injection of pCBWN DNA induced protective immunity, preventing WN virus infection in mice and horses when subjected to challenge with the NY99-6480 strain of WNV (Davis et al., 2001).
  • Related Vaccine(s): ALVAC-WNV-PrM/E (dogs and cats) , West Nile virus DNA vaccine pCBWN encoding prM and E
1. IgG
  • Gene Name : IgG
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 16059
  • Genbank Accession : AF010213
  • Taxonomy ID : 10090
  • Chromosome No : 12
  • Gene Starting Position : 881411
  • Gene Ending Position : 914690
  • Gene Strand (Orientation) : +
  • Protein Name : immunoglobulin heavy chain (V7183 family)
  • Protein Note : Also known as IgG; IgH; VI24H; VH7183; B9-scFv; IgVH1(VSG)
  • DNA Sequence : Show Sequence
    >gi|94393741:881411-914690 Mus musculus strain 129/SvJ chromosome 12 unlocalized genomic contig, MGSCv37 alternate locus group 129/SvJ
    CATGGACTTTGGGCTCAGCTGTGTTTTCCTTGTCCTCATTTTAAGAGGTAATTTGTAGAAATAAGATCCT
    GCCAGTATTGTGTACAGGAGAAATAGAAAAATTTTTCTTTCCTCTATTTTGTTTTGTTTTGTTAGTGACA
    GTTTACAAATAAGCATTCTCTGTTGTGAGGTGCCCAGTGTGAGGTGAAGATGGTGGAGTCTGTGGGAGGC
    TTAGTGCAGCCTGTAGGGTCATTGAAACCCTCCTGTGCAGCCTCTGGATTCATTCTCACTGACTACTGAA
    TGACCTGGATCCTTCAGGCTTCAAAGAAAAGGATGGAGAGGGTGACAATAAAATTTTTCCCACTCACACC
    CACTTGCTGGCCCTGGCGTTCCCCTGTAATGAGGCACATAAAGTTTGCAAAACCAAGGGGCCTCTCTTCT
    CAATGATGGCTGACTAGGACATCTTCTGATACATATGCAGCTAGAGACATGAGCTCCCGGGATACTGGTT
    ACTTCATATTGTTGTTCCCCCACAACAGTTGCAGACCCTTTTATTTCTGTGGGTACTTTCACTAGCTCCT
    CCATTGGGGGCCCTGTGTTCCATCCAATAGCTGACTGTGAGCATCCACTTCTGTAGTTGCTAGGCCCCGG
    CATAGCCTCACAAGAGACAGCTATATCAGGGTCCTTTCAGCAAAATCTTGCTGGTGTATGCAATGGTGTC
    AGAGTTTGGAGTCTGATTATGGGATGGATCCCCAGGTATGGCAAACTCTAGATGGTCCATCCTTTCCCAA
    CAATAATTTTTAATGGTGGAGATAGCACCTACTATCCAGACACAATGAAGGGCCAATTCACTATCTCTAG
    AGATGATGCCAAAAACACACTTTACCTGAAAATAAACAGTCTGAGGTCTGAGTACACAGCCATGTATACA
    TATATTCCTAAGCTTGAGTAAGTGGACTTAAACTGATTCCATCACAACTTGCATGAGATGGATATTCCCC
    AGTGTTAAGACCTGTCACCATCACTGTCAATCAGAAGACAAAGTTTATGCACAACAAAACAAAAAAACCA
    AAAGCAGAGGCCTCCAATTACAAGTAATAGACCCAGACCCACAGTCTCTGAAAACTGACTGTACAGTTGG
    ATCCAGTCTTTTACTTCTTTTCCCTGGATTTTATATTACTGAGGAAATGAGGAAAGCTCTACAATATCTG
    TTCTCCATAGTGCTCAACACCTCCAAGCACAGGTTACCCATATTCATGCCTGCCTTCTGCTACACTTCTT
    GTCTTGTAGACTACTTCAACCTATTTTGTACTCCAGTTAATGAAACTCAAGTCTAGCAGCCTGTCACTGT
    TTATTCTAAAGTATTATGAACAGGTGACCTCCCATCCTTCCCCAACGCAATAATCATATTTAGGAATTTG
    AGGTTTTATGAGATATGATCTCAGGGTAGAGAGAGAAAGCAAACTACATAGAAATATAGACTGACATAAA
    TCAAGACTTGCATAAGCTAGTCCCCAAGTTCCATGTCCCTAAGTGGCAAGGACTATCTTCTGAGCCTAAT
    GAGATGAGATCCAAATCAAACCTCCTGGGTCTTTTTAGATAAACATGTGAGATCAATAGACTAAATGCTT
    TGGCTGGGCTTCCTTGCAATCCAATTCCCAAACAAAAATGGATCTGGCTCCACAGACACCACAAGAATAG
    TCTTAAATAGTTCTTTAAGTAGAATGTCTGATCACTACGAGCCCAATTCCATCCTAAATACTCTTCTGGA
    TTATACATAAATAAAAATTGAACATAGGGCATGGGGCACTGATCTCCCTGTGCTACATGAATGGGGGCTC
    ATTTACTAAATGTTCCCATTTTTCTTTCTAGCGCTGCACAGTGCAAATCCTACAACTTCCTGTTTATCTA
    CAATGTGAACTCCAAACAGTACAAGAAAAAACGTTCCTTATGTTCCTCTCCAGGTTCTCCAACAAGCACA
    GAGCAACCTTCTGTCACCAGGACGGAAAACTGGAAACCTTGCTCACTGCTTCCTTTTATTCCCTCGGGAA
    CCTCCCCCAATGCAAAGCAGCCCTCAGGCAGAGGATAAAAGCTCACACAAAGACGAGAAGCCCCATCCTC
    TTCTCATAGAGCATCCATCAGAGCATGGCTGTCCTGGGGCTGCTTCTCTGCCTGGTGACTTTCCCAAGCT
    GTAAGTGTTTCAGGGTTTCAGAAGAGGGACTAAGACATGTCAGCTAGAAGATGTGTGACTAATGGTGATG
    TTGCTTGTCCCCAGGTGTCCTGTCCCAGGTGCAGCTGAAGGAGTCAGGACCTGGCCTGGTGGCGCCCTCA
    CAGAGCCTGTCCATCACATGCACCGTCTCAGGGTTCTCATTAACTAGCTATGGTGTACACTGGGTTCGCC
    AGCCTCCAGGAAAGGGTCTGGAGTGGCTGGTAGTGATATGGAGTGATGGAAGCACAACCTATAATTCAGC
    TCTCAAATCCAGACTGAGCATCAGCAAGGACAACTCCAAGAGCCAAGTTTTCTTAAAAATGAACAGTCTC
    CAAACTGATGACACAGCCATGTACTACTGTGCCAGAAACACAGTGTGGGAAGTCCAATGTGAGCCTGCAC
    AAATACTTCTCTGCAGGGATGATCACAACCAGCAGGGGGCGCTGATGACCCAAAGGGACTTCCCAGGATC
    TCTTCTGGAATCTAGGGAGTTCTGGCCTGTGTCTATCAGCATGTGTTTCAATGTTAGAGTTGTGAGTTTT
    CCTTCCAGCAACAGAGATATTTTAGAGCCCACTTTTCATGGTCATTCTACTAAATTTGTTCACATAGTGG
    AAAGATTTGTTAAATGATTCTATAGTCTAATAGGGTCAAACAAAAACAAATAATTGAGTTCATATCTACC
    AAAAAAAAAAAAATTCCCTCAAAGTGGACAACTGTGTAGGTGAGGAAAACCAGGGGGATTTGGGAATAGA
    TTATTTCTCTCCCGACTGTGGTGTTAGTCACCTTTCAGCCATTTACTGTATTTAATTCATGTTTAAAGTT
    AATTGTATTCATCTTCCCTAACATGAAGTTTTCAAACACATGTCCACAATTTAATGATGACACAGTTATC
    ATTGTGAATGATAACTCATAAGATCTCTCTCCATATATGAAACACACGATATTCTGTTATTAGCTATAGC
    CAACAAAGTTACATATCATTATTATTACTGAAATAATTCTTCCCATCTAACTGAATAGTTTTCTCACTCG
    ACACTGCCTATGCTGCGATCAGCCTGCTCTAATTTTACCTTTGCTCAGAGCACTGCTTTCTGTTTCATTT
    GATAAGATGGTGCCTGGTTGTCACTGAAAATGTGTCCTCCAGTTTCACAGTGATTAATGTGATTTTCAGT
    ACATTGAGAACAGAGCCACAGCAAAAATGAGATGGAATGTCATCATTTTTACGCCAGGTGCTGCAGAAAT
    AGCTAGGTGGTTAAGAGAGAATATTGAACTTTGAGGGGTTCAGATTAAATTCCTGATACCCACAATGTGC
    ACCTCATAACCACATGTACATATAGAAAACTCAGTATAAATGTGGCCTCCGTGAGCACCACACTACTCCC
    ACAAACACATATACACATAATTAAAAGTAAAGATTTTAGAAAAATGGCTAATCTAATGATAGGAAGTAGT
    CAAAAAGAGAGTTCTTTTGTCATGTACATATGTGTAGCAGACTTAAATGTTAAACATTCAAGAATACATT
    CCTCGATCCACATTAAAATTTTGCAAAGAGTAGCACAGACGGTGGCAATTGCTAAACTTATATCTAGAAA
    CACAATTATGTGTGGTGATATTTAATTACACATTTATACCAGGACATATGACAATATGGAAACCAAACAT
    GTTGTATCCACATGCTCTAAGGAAAACTAAATGGAGTGTGATAAAACCAAAGAAAATGTGAATATGAAAT
    ATTTTTCCAACTCTGCATCTTAAAACGGTTTCTTTCATGTGTCATATCTGCTATGAGGACTTTCTTCTGC
    CCATGTCCAACTCCAGAGCATGCCACAGCAGGAAGACCTACAGGTATTACTTCTCTGCACCCAGGAAAAC
    CACCTCTGTCCTGACCCTGCAGCTCTCAGAAGAGCCCAGACCTTCATTCTCAGGCCCTCATCCAGTAATC
    AGCACTGAATACAGAGCACTCACCATGGACTTTGGGCTCAGCTTGGTTTTCCTTGTCCTTATTTTAAAAG
    GTAATTCATAGAGATAAGATTCTATCTGTTTTGTGTACATGAGAAACAGAAAAATTGTATTGTTTCTCTA
    TTTTGTTTTGTTTTGTTAGTGACAGTTTCTGACTCAAGATTCTCTGTTTGAAGGTACCCAGTGTGAGGTG
    AAGCTGGTGAAGTCTAAGGGGAGGCATAGTGCAGCCTAGAAGGTCCATGATACTCTACTGTGCAGCCTCG
    GATTCACTGTAAGTGACGACTGGTTTGTCCGTGTTTGCCAGGCTCCAAAGAAGGGGCTGCAGTGGGGGAT
    GGGAATAATTTTTCATGGTTGTGGTAGCCCCTCTTATGCAGACACCTTGAAGAAGTGGGTTGGACGTAAC
    ATATTCAGAATCAATATTTAAAGATTCTAATCCTTGAAGATATCACTTTTGACCAAGTATATATGAACCA
    TGTTACTGAGGTTTATGGAGGTTTGAGTATGTTAGGTCCATGGATAGGGAAAATATTAGGGGATTTTAGG
    AGTAACTGAGGCTTGTTGTAGGAAGGACATCACTGTAGGGGTAGGCTCCGTGTTCCTATCTTCAAGCTCT
    ACCCAGTGCAGAATAGAGCCCTCTTCTGCCGGCAAGTGGAAAGAGTTTCTCTTCCTGGCTGCCTTCAATC
    CAAGTTGTAGAATATCAAATCTCCTAACACTATGACTGCGAGCATGCTGACATGCGTCCCACCATAAAAA
    TAGACTGAACCTCTGAAGCTTTAAGCCAGCCTCTAGTAACTGTATTCTTTAATAAGACTGAACTTGGCTA
    TGGTGTCTTTTCACAGTAAAATGGAAACATAGACAAGGTTCTAACTCTCTGTACTAGAGGACCATCTCTA
    TGTCCTTGGTGTTGTATGTAAATTATTGAACAAATACTATAGACAAGTTGTATGGCCAAAAGTCCATCCC
    CTTCAACAATCTACTATCTGGAACCATATAGATTAGATTCCTTTCCTGCACTCATTTCCCTTACTTGCTG
    AGACATTTTGAAGACATGCTCAGAATCCCTGAACTTCCTGCTGAAAAAAAAATACCCCTCCAATTTGAAG
    ACAGTTCTCTTCCAAAATTCATCATAAATACTGATCCACATGTCCAGGCATATCATGTAGTTTTAAAAAA
    CAAACCAATCAATGCTAAAGTGGGTAAGTGCCTACATCATTGGTTTATGTCTGTTCATAACCTGGTATAT
    AGCTAGAGACCAGGACTGCATGTTTCTCCTAGGCCACACCTCTCCCACAAATGCTGGCTCTGCCTCTCCA
    GAATTCCAAGATCATGGATCTCTGGGTCCCCAAGGAACAATAAGTGTGCACTCTTGCCAGCCTGTACACT
    ACTGCACTAGCTTCTCCCCCTGGAGCTTGGTCATTGCTCAATCTTCCCTTTCCAAAGCCTGGCCAAATTC
    CTCCTACCTTTTGTTCTTTCAGTCAGGCCACCTAAGTCATCTTGAATGAAAAACAACACAAAATCTGAAC
    TTAAAATCAACAAATAATACAAGTGCTGCGCACAAAATCAATCATTCTAAACTCATCAACTATTTTATGA
    TGGAAATCTTCCAACATACAAGCTACCACCAGGTCTAAGAATTACTCATCTACATGTTGCTTCCTCTCAC
    TCACAGCCTAACCATAAAAGGGCTGTTTCTTCCTCCCATGTCCCCTCTTTTGCCTTCAGAAGCAGAAGCT
    CCACCTCCTCCTCTTTGCCCAGCAATTGGCTTCTTGTCGTCTTTATTATCATATTAATTACTTAGGGGAA
    AATCCCGTGTAGTGGCTATTCCTGGTTGTCAACTTGACAATATTTGGAATGAACTACAATCCGGAATTGG
    AAGGCTCACCAGTGACCCTTATCTGGAGGCTTGGAGATCCTTATCTGGATCTTGGTTTGAAGATCTTGAG
    CCATAGGGGCTATGGATTCCAGAAGATTGAATCTCCGAGTTTAAGGAACACACCTTTAATCTGGGCTACG
    CCTTTCATCTGGGATTAAAGGTGTGGCGGAACACACCTTTAATCTGGACTACACCTTCTGCTGGAGACAA
    TATAAGGACATTGAAAGAAGGGAGTCTAGCTCTTGCTCTTGCTCCTTCGCCTGCTTGCTGCGTGAGACTG
    AGTAACTGCTAGATCCTTGGACTTCCATTCACAGCTGCGACTGAACAATTGTTGGGAATTGGGCTGCCGA
    CTCTAAGTCATCAATAAATTCCTTTACTATCTAGAGACTATCCATAGTTCTGTGACTCTAGAGAACCCTG
    ACTAATACAGAAGTTGGTACCAGGAGTGGTTCTAGAGTAACAGAAGTACAAGGATGAATCTTTTAAAATA
    CTGGAATTGGCTTGTTGATCCACCAGCACTTTCAACTATTGAAACCTCTCCAGATTCTCTCCCTCCTGGG
    AGCTCAGAGAATTTTGAAGACCCATGGTTGAAACTATATTCCGAACTTAAAGAAGCAAATGCCCTTGATT
    TTCTTAATGAATTAGGTGATTCAGTGCACAAAGCTTTCTACAAGATGGGGAAAAAATTGGAAAATGATTT
    TACTGGCTGGCTGCTCTTAGTATCTGTGGAAAAAATGATGAATGAAAGGAAGGAGTTGTGTGATAAAATC
    GAAAGGCTCCAGACACAAGTAAACGATCTAAAAGTTGCTAAGTGTGTCCTTGAGGAGAATCTTCTCTCTT
    GTAGCAATAGAGCTCAAGTTGCAGAAAATCAAACAGAAACTCTCATTGTAAGGTTGGCTGAACTACAGCG
    AAAATTCAAGTCTCAGCCTCAGAGTGTGTCAACAGTTAAAGTAAGGGCTCTAATTGGCAAAGAATGGGAT
    CCTACAACATGGGACGGGGATGTGTGGGAAGACCATGTTGAAGCTGAGAATTTTGAATCTTCAGATTCTC
    AAGGGTTTGCCCCACCTGAGGAAGTAGTACCCTCAGCCCCACCCCTTGAAATAATGCCTTCCCCACATGA
    GGAAATTAATTTTGCAGAGTCTGATAAACCAGCAATGATTTTCACTACTGATGTTTCTCAAGGCCCACCA
    ATAGTTTCTTCTAGACCTGTAACCAGACTCAAAGCAAAACAGGCTCCTAGAGGGGAGGTAGAAAGTGTAG
    TCCATGAGGAAATTCGCTACACTACTAAGGAGCTTAATGAGTTTGCTAATTCATTCAAGCAGAAACCTGG
    TGAATATGTGTGGGAATGGATTTTAAGGGTGTGGGATAAGGGTGGAAGGAACATAAGACTAGAGCAGGCT
    GAGTTTATTGACATGGGTCCTCTGAGTAGAGATTCTAGGTTTAATACGGAAGCTCGCATAATTAAAAAAG
    GTGTCAAAAGTTTGTTTGAATGGTTGGCTGAGGTGTTTATCAAAAGATGGCCTACTGGAAATGACTTGGA
    GATGCCTGATATTCCGTGGCTTAGTGTTGATGAAGGGATTTTAAGACTTAGGGAAATTGCAATGCTAGAG
    TGGATATATTGTGTAAAGCATAATTGTCCACAATGGGAAGGTCCAGAAGATATGCCTTTCACTAGCTCTA
    TAAGACGCAAATTGGTGAGAGGGGCACCAGCACATTTGAAGGGTTTTGTTCTTTCCCTTTTCCTTGTACC
    AGATCTTAGCATTGGAGATGCTTCTGCTCAATTAGATGAATTAAATTCACTGGGTTTAGTTGGATTCCGA
    GGTAACAAGGGCCAGGTGGCAGCATTGAATCGCCGGAGACAAGGTGATTCTAGTTATTATAATGGACAGC
    GTAGACAAAAGAATGTTTATAATAACATACCCAGCAATGGTCAGCACAGGAGAGGTGAAATTTATAATGG
    CATGACTCGGTTGGACCTTTGGTACTGGCTAACCAATCATGGTGTTTCCAGGAATGAAATACATAGGAAG
    CCTACTGCATATTTGTTTGATCTGTATAAGCAGAAAAATTCTCAAACAAATGAAAGAAAGGCTACATTAG
    ATCATGGTAAACAGCAATCTCGGCCAGTGAATCAATTTCCAGACTTGAGACAGTTTGCAGATCCAGAACC
    CCTTGAATGAAGGGGTGGCCAGGTTCCGCTGAGGAAGGATCTTGATAAGACACCCAAAGGTTTTGCTGTT
    ACCCTTTCTCCAGTTCTTCCCCAGAGGGACCTAAGGCCTTTTACAAGGGTAACTGTACACTGGGGAAAAG
    GAAATAATCAGACTTTTCAGGGTCTGCTGGATACTGGTTCTGAGTTGACACTGATTCCAGGGGATCCCAA
    GAAACATTGTGGCCCTCCAGTTAAAGTAGAGGCTTATGGAGGGCAGGTGATTAATGGAGTTTTGACTGAT
    GTCCGACTCACAATAGGTCCAGTAGGTCCCCAGACACATCCTGTGGTGATTTCCCCAGTTCCAGAATGTA
    TAATTGGGATAGATATACTCAGAAATTGGCAGAATTCTCATATTGGTTCCCTGAACTGTAGAGTGAGGGC
    TATTATGGTTGGAAAGGCCAAATGGAAACCTTTAGAGTTGCCTCTGCCAAAGAAAATAGTGAATCAAAAA
    CAGTATCGTATTCCTGGAGGCATTGCAGAAATTACTGCCACTATCAAGGACTTGAAAGATGCAGGGGTGG
    TGGTTCCCACCACATCTCCGTTTAACTCTCCTATCTGGCCAGTGCAGAAAACAGATGGATCATGGAGAAT
    GACAGTTGATTATCGAAAACTAAATCAGGTAGTAACTCCAATTGCAGCTGCTGTACCAGATGTAGTTTCA
    TTACTTGAGCAAATTAACACATCTCCTGGCACCTGGTATGCGGCTATTGATCTGGCAAATGCCTTCTTCT
    CAGTACCTGTCCATAAGGACCACCAGAAGCAATTTGCTTTCAGTTGGCAAGGCCAACAGTATACTTTCAC
    AGTTTTGCCTCAAGGATATATTAACTCTCCTGCCCTGTGTCATAATTTAGTTAGAAGGGATCTTGATCGT
    TTGGATCTTCCACAAAATATCACATTGGTGCACTATATTGATGACATTATGCTGATTGGACCAAGTGAGC
    AGGAAGTAGCAACCACTTTGGACTCATTGGTAACACATATGCGTATCAGAGGATGGGAAATAAATCCAAC
    CAAAATTCAAGGACCATCTACCTCAGTGAAATTCTTAGGAGTCCAGTGGTGTGGAGCATGCAGAGATATT
    CCTTCTAAGGTGAAAGATAAGTTATTGCACCTGGCCCCTCCTACAACCAAGAAAGAAGCACAACGTTTAG
    TGGGTCTATTTGGATTCTGGAGACAACACATCCCTCACTTGGGTGTGTTACTTAGGCCTATTTACCAAGT
    GACTCGGAAAGCTGCTAGCTTTGTGTGGGGCCTGGAACAGGAGAAGGCCCTTCAACAGGTCCAGGCTGCT
    GTGCAGGCTGCACTACCACTTGGACCATATGACCCAGCAGACCCGATGGTACTTGAGGTGTCTGTGGCTG
    ATAGAGATGCTGTTTGGAGCCTCTGGCAGGCCCCTGTAGGTGAATCACAGAAAAGACCTTTGGGATTTTG
    GAGCAAAGCTCTACCATCATCTGCAGACAACTATTCTCCCTTTGAAAAACAGCTCTTGGCCTGCTATTGG
    GCCTTAGTGGAAACTGAACGTTTGACAATAGGACACCAAGTTACTATGCGACCTGAACTACCCATCATGA
    GCTGGGTACTATCAGACCCTGCAAGTCATAAAGTGGGACGCGCACAGCAGCAGTCTGTTATCAAATGGAA
    GTGGTATATACGTGATCGGGCCAGAGCAGGTCCTGAAGGCACAAGCAAGTTACATGAAGAAGTTGCTCAA
    ATGCCTATGGTTTCTACTCCTGTTACACTGCCATCTGCTGCCAAACATGTGCCTATAGCCTCATGGGGTG
    TTCCCTATGATCGACTGACCGAAGAGGAAAAGACTAGAGCCTGGTTTACTGATGGCTCTGCACGTTATGC
    AGGCACCACCCAGAAGTGGACAGACAGCTGCAGCATTACAACCCCTTTCTGGGACAACCCTGAAAGACAC
    AGGTGAAGGGAAATCTTCACAGTGGGCAGAACTTCGGGCAGTACACATGGTATTACAGTTTGTTTGCAAG
    AAGAAATGGCCAGATGTACGATTATTCACTGACTCATGGGCTGTAGCCAATGGATTGGCTGGATGGTCAG
    GGACTTGGAAAGATCACAATTGGAAAATTGGTGAGAAAGACATCTGGGGAAGAAGTATGTGGATAGATCT
    CTCCAAATGGGCAAAGGATGTGAAGATATTTGTGTCCCATGTAAATGCTCACCAAAAGGTGACTTCAGCT
    GAGGAGGAGTTCAATAATCAAGTGGATAAGATGACCCGTTCTGTGGACAGTCAGCCTCTCTCCCCAGCCA
    TCCCTGTCATTGCTCAATGGGCACATGAACAAAGTGGCCATGGTGGTCGAGATGGAGGTTATGCTTGGGC
    TCAGCAACACGGGCTTCCACTCACCAAGGCTGACCTGGCTACAGCTGCTGCTGATTGCCAGATCTGCCAA
    CAGCAGAAACCAACACTGAGTCCCAGATATGGCACCATTCCTCGAGGTGACCAGCCAGCAACCTGGTGGC
    AGGTTGACTACATTGGACCACTTCCTTCGTGGAAAGGACAGCGTTTTGTTCTTACTGGAGTAGATACTTA
    TTCTGGTTATGGATTTGCCTTTCCTGTACGTAATGCCTCTGCTAAAACCACCATTAACGGACTGACAGAA
    TGCCTTATCTATCGTCATGGTATTCCACACAGTATTGCTTCTGACCAAGGAACTCATTTCACAGCCAGAG
    AAGTACGACAGTGGGCCCACGATCATGGAATTCACTGGTCTTACCACATTCCCCATCATCCTGAAGCAGC
    TGGTCTGATAGAAAGATGGAATGGCCTTCTGAAGACGCAGTTACAGCGCCAATTAGGTGGTAACAGCTTG
    GAAGGCTGGGGTAGAGTTCTTCAGAAGGCAGTATATGCTTTGAATCAGCGCTCGATATATAGTACAGTTT
    CACCCATAGCCAGGATTCATGGGTCCAGGAATCAAGGGGTGGAAAAAGGAATAGTTCCACTTACTATCAC
    TCCTAGTGACCCTCTAGGAAAATTTTTGCTTCCTGTCCCCATAACTCTAGGTTCTGCTGGCTTAGAAGTT
    TTGGCTCCAGAGAGGGGAGTGCTCCTACCAGGAGCTACAACAAACATTCCATTGAACTGGAAGCTCAGAC
    TTCCCCCTGGTCATTTTGGGCTTCTAATGCCCTTAAACCAACAGGCTAAAAAAGGAGTAACAGTGTTAGG
    AGGGGTGATAGATCCAGATTACCATGGGGAAATTGGATTACCTCTTCACAATGGTGGTAAGCAAGATTAT
    GTCTGGAGTGTAGGAGATCCCTTAGGGCGTCTCTTAGTACTACCATGTCCTGTGATTAAAGTCAATGGGA
    AACTACAACAGCCTAATCCAAGCAGGATGACAAAGGACACAGACCCATCAGGAATGAAGGTATGGGTCAA
    TCCTCCAGGAAAAGAGCCAAGACCTGCTGAGGTGCTGACTGAAGGAGAAGGAAATATAGAATGGGTAGTA
    GAGGAAGGTAGTTATAAATACCAATTAAGGCCACGTAACCAGTTGCAGAAACGAGGATTATAAAGTAATA
    TGAATGCCCATTGTAAATTTACTAATGCGTTTGCGATTGTACGAGGGATAGTTATATCATGTTAGGCGTA
    TTTACAAACTTGTTATTGTTTTATGTGAACATGAGATATTATTTGTGTCAAGTTGACAAGGGGTGGATTG
    TAGTGGCTATTCCTGGTTGTCAACTTGACAATATTTGGAATGAACTACAATCCGGAATTGGAAGGCTCAC
    CAGTGACCCTTATCTGGAGGCTTGGAGATCCTTATCTGGATCTTGGTTTGAAGATCTTGAGCCATAGTGG
    CTATGGATTCCAGAAGATTGAATCTCCGAGTTTAAGGAACACACCTTTAATCTGGGCTACGCCTTTCATC
    TGGGATTAAAGGTGTGGCGGAACACACCTTTAATCTGGACTACACCTTCTGCTGGAGACAATATAAGGAC
    ATTGAAAGAAGGGAGTCTAGCTCTTGCTCTTGCTCCTTCGCCTGCTTGCTGCGTGAGACTGAGTAACTAC
    TAGATCCTTGGACTTCCATTCACAGCTGCGACTGAACAATTGTTGGGAATTGGGCTGCCGACTCTAAGTC
    ATCAATAAATTCCTTTACTATCTAGAGACTATCCATAGTTCTGTGACTCTAGAGAACCCTGACTAATACA
    TCCCTACATACAGGAAACTTGATGTATAAGTAAAGAAAATAGTAAATCTAAAAATTTCCTTATCAAATAC
    ATGCAAGAAATCCAAAATACCATGAAAAGACCTGATCTAAAAATAGTAGGAACTGAAGGTGAAGTGTCCC
    AGCTCTGAAAACTAGAAAATGTTTTCAATATTTTTCCTAACAGTGAAGACATGGATCTAATGAGGCCACC
    TCTTATAGCCATGCAAGACTGACAGTGGAGGGATAAGGACACCAATCCACCCACAAAACTTTTGACCCTA
    AATCAGTTTTATCTAAAAGCAATGCAGGGGCACAAATGGAGCAGAGACTGGAGGAATGGTCAAACAATAA
    CCTGTCATATCTGAGACCCACCTAATTGGCATACACCAGTCACTGACATTATTAATAATGTTCCATTATG
    CTTACAGGCATTTCTCTAGCATTACTATTCTTGGAGAGACTTCACACAGCATCTTATTGAAACAGATGCA
    GACACCCAGAACCAAACATTGGATGGAGATTGGGATCCTTAAAGAAGAGTTGGGAGGATAATTGAGAGAC
    CTCAAAGGAATAGCAACCCCATAGAAAGACACGAACAGGGTCAGTAAACCTGGACCCATGGGGTATCTCA
    GAGACTGATCACCAACCAAAAATCACAGAGGGCCTGGATTGATTCCCCTGGCACACATGTAGCAGAGGTC
    TGCCTTGTCCTTCAGTAGGTGAAGATGAGCCTAAGGCTTCAGAGACTTGATATATCAGCATACAGCAACA
    CCCAAGTGTGTCCCACTATCTCAGAGGTGAAGGGGTGGAGATGGGCAGAAGGGTCCTGATAGGGGACAAC
    TGCAAAGAGGCAATATTTGGGACAGAAAGAAAGGAAGAGAGAGGAAGATAAAGAGAGAGATGAAGGAAGG
    AAACAAACAAACCAAGATGAAGAGAGAGAAAAGGGGGAAAATAGCCTTGAATGGTTCAGGGATTCAAAGG
    GACATACCTAAGCATGGTAAAACAATGCACATAATGGCAGCAAGTAGCTAACACTGAATTAAATAGAAAG
    ACACATAAAGCAGTTCTACTAAAGTAAGAGACAGAGTTGCCCAATCTCACCCTATTTATTCAATAATAAT
    GTACTTGAAGTTCTAGCTAGGGCTGTAAGACAACTCAAGGAGATCGGAGGATACAAATTAGAAAGAAAAA
    TTCAAAGAATTGTAATTGGTAGATGATAGGATAATATACATAAATGACCTCAAAATTCTTCCAGAGAACT
    CTGAAAGCTGATAAATACCTTCAGCAAAGTGGCTAGAAACAAAATTACTTCATAGAATTCAGGAGCTATC
    CTTTATAGAAAAGTTAAAGTGGCTGAGAAAGAAATTAGGAAAATCACATTCTTTGCAATAACCAAAAATA
    ATATGAATTAGCTTGGTGTGACTCTAATCTTGCAAGTGAAAGATGTGTGTGACAAGAGCTTCAGGACCCT
    GAAGAAAGAAATCAAAGAACTCAAAGATGCAAAGTACTCTAATGCTCATGGATAGGCAGAATTAACATAA
    TGAAAATGCCAAATTTAACAATTCAATCTACAGATTCAGTGGAATTCCCATTAAATATCCAACCCAATTT
    ATTACATTCTTGAAAAAGCAAATCTCAACTTCATATAGAAAAACAAGAAATTGAGGGTAGCTAACAAAAT
    CCTGAACAATGAAAACACTTCAGGAGAATTCACCATCCCCTACCTCAAGCTGTATTTTAGAGCAATAGTT
    ATTAAAACTGCATGGTATTTGTATAGAAACAGATATGATGATCAATGTAATTGAATTGAATACACTGACA
    TAAAACCACACTGTTATGGACACTTGATTTTTGACAAAGAACCCAATAATCATAATAAAAATCATAATAA
    GAATGCATCCCCCAACAAATGGTCCTGATCTAAATGCAAATAGATTCATATCTATCATCCTGCACGAAAT
    TCAAATCAAAGTGAATTGCAGACTTCGACCTAATACTGGATTAACTAAATCTAAATGAACAAAAAGTAGA
    GAATAGTTTTGAACTCATTGATGCAGGATTCAATTTCCTGAACAGAACCACAATGGCTCAGGCTCTAGGA
    TCATAAATTGGTAGATAGGATCTCATGAAACTGAAAAACTTCTGTAAGGCAAAGGCAATAAAACAAAATG
    GCAACCTACAGATTGGAAAAAAAATAATCTTCAGTATCCCTAAATCCCATTGAAGGCCAATATGCAAAGT
    ATATAAAGAACTCAAGATGTTATCCTCCACAAAACCAAATAAATCAATTAAAAATGAACTACAGAGCTAA
    CAAGAGAATTCTCAACAGAGGAATCACCAATGACTGAGAATCACTTAAAGAAACATTCAATATTTGTAGT
    CACCAGAGAATTGCAAATCAAAACTACCCTGAGATTCTACTTTATACCAATCATAATGGTCAAGATAAAA
    ATTCAAATGACAGCGCATGTTGGTGAGGATGTGTATACTTTTGCATTGCTGGTGAGGAAAACAATCTGGC
    AGCTCCTCAGAAAATTGTAAATAATTCTACCTGAAGATCCAGCCATACCACTCCTGTGCATATACATAAA
    ATGTGCTCCACCATACCACTAGGAGATATGTGCCACTATGCCCATAGCAGCCTTATTTGTTAATAGCCAA
    AAGATGGATACAACCCTGATGTGCCTCAAACAAAGATTGTATATAGAAAATATGGGTTCCCTTACACAAT
    GGTATTCTACTCAGCAATTAAAACGTGAGAACATCATAAAGTTTTCAGGCAAACTGATCAAATGAAAAAG
    TATAATCTTGAGTGAGGTAACAGAACCAAAATGACCTGCATGGGATGTACTCACTGGTAAGTGAATATTA
    GACTAAAAGTATAGAATATCAATGATGAAAGCCACAGACCATAAAGAGTTTAATAAGATGGAAAGCTCAA
    GTACGGATTCTTCAATCCAATATAGAAAGAGGGACAAAATAATCAGGGGAGGCAGAGGGAGAGAGAGACA
    TTTGGTGGAAATGGGAGAAGAAGGGAGAAAGGCAGAAAGGATCAGGCGTTGGGGAACACTGGAAAGCAGC
    CCAGGGGTCCTGGTAAATGGATTAAATATTCAGCTGAATGGAGGTGGGAGGCAGGGGGAAGCTCTGCAAA
    GTCCAAGAGACCTGGGATGTGAGAGGCTCCCCAGATGATAATCTTAGCCTTCATGCCTAACAGTTGTAGA
    TAAACCCTGAAGAGATCACTTCCAATAGATGCAGAGGGCCCTAAGTGGTTGGATGGAGTCCCCCAACTTA
    CCTCAAAATTGTCAATACTCATAGAAATTAGGACAATGAAAATCAAAACACCCTGAGATTGTATCTTATG
    TCTGTCACAATGGTTAAGACCAAAACCTCAAGTGATGGCTTGTGCTGGCAAAGATTCAGAATAGTAAAAG
    TCTCCCCATGGCTTGTGGGAATGCAAACTCTTACAACCTCTTTGGAAGTATATTTGATTGTTACCTGGTA
    TAAAATGGCAAAAAAAAAAAATGGTTGAAGGGGGACTAAAAAAGGAAGAAAGGGGAGAACTATGGGATGC
    GAAACAAGAAAGTTTGTTGCAAAAGAAATATGTTTCCACTGCAAACCCTGAGTCTCAGACAGAAGGGGAC
    CTGGAATTCTTCAGATACAAAGAATCTCTAAACCCTGAGGACATTCTATCACAAATAAGTAAAATTCAGA
    AAATTCTGAGTGCTCCCATCACGGAGATGAATCTGCTATGAACAGCTCATAGGTGTGACCCTCTACAAAA
    GCCATATTATTGAAAAGCCACATTGTGCCCAGACTTTGGAAAGACTGAGCTCATATCCTGAAATACAGTT
    ATGTGTGGTTCTATTTAATTACACATTTACACTAAGAAAACATGGCAGTATGGGAATGAAGCTTGTTCTG
    TACACATTAACAGAGGGAAACTAAACAAAGTATGGTGAATCCCTAACCAAAAGTAAAAAAAAAAAAAGAA
    AGAAAAGAAAATAAAAGTGAAACTACAATATGTTTCAAATGCTGTAACTGAAATCTGGTTTTTTGATGCT
    TATATCTGGTATCATCAGTGACTTCAGATTTAGTCCAACTCCAGAGCATGGTATAGCAGAAAGACATGCA
    AATAAGCCTTCTCTCTGCCCATGAAAAACACCTCGGCCCTGACCCTGCAGCTCTGACAGAGGAGGCCAGT
    CCTGGATTCGATTCCCAGTTCCTCACATTCAGTGATCAGCACTGAACACGGACCCCTCACCATGAACTTG
    GGGCTCAGCTTGATTTTCCTTGTCCTTGTTTTAAAAGGTAATTTATTGAGAAGAGATGACATCTGTTGTA
    TGCTCATGAGACAGAAAAATTGTTTGTTTTGTTAGTGACAGTTTTCCAACCAGTATTCTCTGTTTGCAGG
    TGTCCAGTGTGAAGTGAAGCTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCTGGAGGGTCCCTGAAACTC
    TCCTGTGCAACCTCTGGATTCACTTTCAGTGACTATTACATGTATTGGGTTCGCCAGACTCCAGAGAAGA
    GGCTGGAGTGGGTCGCATACATTAGTAATGGTGGTGGTAGCACCTATTATCCAGACACTGTAAAGGGCCG
    ATTCACCATCTCCAGAGACAATGCCAAGAACACCCTGTACCTGCAAATGAGCCGTCTGAAGTCTGAGGAC
    ACAGCCATGTATTACTGTGCAAGACACACAATGAGGAAATGTTACTGTGAGCTCAAACTAAAACCTCCTG
    CAGAGCACCCAGGACCAGCAGGGGGCGCAGAGAGCACATGGAGTTCTGATTCACAGAAGAGTTACAGCCT
    GTACAATTAGACCCAATCTTCAACAAACCGTCAAAATATTCGATCCAAAATTGTTCCTGTCTAAAAGTAA
    TTCAAGGACAAAATGGACCAGAGACTGAAGAAATGGCTGACCTGTGACCCTCCCAACTTTGGATCTATCT
    CATAGGCAGGTACCAAACCTTGACATTTGTCACTGACACTGTATTGTGCTTGCAGACAGGAGCATAGCAT
    GGCTGACCTCTAAGAGGCTCTGCAAGCACCTGAATGAGACAGATGTAAATAGAGTGTACAACTGGATTAA
    GTTTGAAGACTGCAATGGAAGAGTTAGAGGAAGGAATGAAAAATCTGAAGGGGATCACAACCCCAGAAGA
    AGACCAACAGTGCCAATTAAACTGGATGCCTGGGAACTCCCAGAGACTAAGCCACAAACCAAGAATCATG
    CAGGCTGGTCTGAGAATCCTGGCACCCAAGTCTCAAGGAACTGCCTTTTCTTGGCTCAGATGGGAGAAGA
    TGAGCCTAAAGCTTTAGACTTGACGCCCCAGGGATGGGCAATACAAAGTTGAGTTTCTTGGGAAAGTGAA
    GAGGATGGTGGGAGGAGGAATAAATCTGGGAAGTGGGACTGGTTGGGGACAACATATTGGTCCTAAATTT
    ATGAAATAATTATCTAATTGATAAAAAGAGTCCTTGGGGTAATGGAGGGCTAGACTCCTCTGTGCCTAGT
    TTGTAACTCTACAGGGATCCTCTTTAAAAGAATAGGGTGCACATAGAGTATATGTGTGTGACACTAATAC
    AGGGGTAAGTGTTTCTGTAAGAACTTTATGAATAAACTTTATTAAAACATCAAAAAGTATAGGTTGTAGC
    AACCCTTGACCTGTACGAATGTTTATAAAACTTTCTATTTTCCTTAATTATATCTGTTTTGCATTTGTTT
    ATTTATTTATTTACTTACTTACTTATTTATGATTTCACTGTGTCTTTCTGTAGTCCTGTATGTGTTTATT
    TGTCTCTTTATTGCTCTGTTTCTGTTTCTTTCTCTCTGTCTAGTATTGTATCTCTCTGTGTCTCTATGTC
    GCCGATTGTGTCTGTGTGTATGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGCATATTGAAA
    TGAGATCTCTTCTTCTATCAGTGTACATAATGACTTTGAAATAAAGTCCATCACTGGGCTTGGATATCAC
    TATCTTGTTAGAATGGTTGCCCAAAGTGTTCCAACCATCACACTGTTTCTACATATAATAGATGGGTTTA
    TTGATTTACTACCAAAACTACCCCATCTTAAGTTATGGATATTAAACACAGATCCTCATGGTGTGTTAAG
    AACTTGAAGCACAGAGCTATATGTACAGCCCACTAAAAATGACTTAAATATAAGATAAACTCTGGCTTGA
    ACAAAACACAGAGCATCACACGAGGCAGAAGTGAATCTCTATGAGGACCAGGATCACATCCCAAAGAACC
    AAAGAACACTTGAGACTGTGGAACCCTAGAGTCAGGGCTGACACTCAGTAAGATTTACTTCATAGAGCAT
    GATGTGGGATTCAAGAAGAAATCAGGCAGGGCCTGTGACCCATGAACCAGATGACTTCCAGTCTCTCCAT
    CATCCTCACACAAACCATAGGCAACAGCTCAGCACTGACTCACCTGTGATGCTGGTGACAAAATGTGTGC
    AAAGCCTCAGAACTGAGACGTGAGGCCAATGTTGCTACCGACACTCAGTGAGCTTCAATTTGCTGCAAAC
    TGCTCCAAAACAACTCAAAGGGTAACTTCTTCTTTTTCTATTTGTACTTGTGATGCCTTGGTAGATATAG
    TTCCCCAATAATTTAATAGGACAAATCATTTTTCCTTTTAACACATTAATCCCCTTTCCTTCCCCCAAGA
    TTCTAAAATTTTTCTTTAACACTGATGTCTGAGAGATATGGCATAATAGATGTTTGTCTTATTCTGAGTT
    GTTCCTTATCAAAAGAAATCAGCTGTGGCACTTTGAACCTAAATATAACAATATTTCACAAAGGCATTCT
    GGGAATATATAGATGGTATTGCTACAAAAGAATAGGAGGATCTATGGCCATACCACCCTTAATGAACCAG
    ATACTATCTAAAAGATTAGGACAGCTGGGCATGTTGGCACAGGCCTTTAATCCCAGCACTAAGGAGGCAG
    AGGCAGGCAGATTTCTGATTCGAGGCCAGACTGGACTACAAAGTGAGTTCCAAGACAACCAGGGCTATAC
    AGAGAAACCCTGTCTCGAAAAAACAAAACAAAACAAAACAAGAGTAGGAGGGTATTAGATGCGAGGTGAT
    GATGGCCATTCAATCAAACCAGAATGTGACCTGAGAAAAGGTCTAAGTTTGTCAGCTTGTCCTGGAGATG
    TGTTGCCTCTGATAAATGCAGAGCTGGAACTGCAATACATTGGATTCCTGTGAGTTACGGAGAAATAAAA
    GGAATAGCCTCTGTTTCCTTTGGTTCATCAAGTTGGCAGTGAGCTAGAAGATGATACTGGGAACCATCAC
    ATGTACTTCTACAGAGTTATTCTACATTCTACAAGTCAGTCTTGCTTGCTTTCGTTTCTGTGAGGAGCTA
    AATACAGAATGTTTTCAATGTCTCATAATGTTCTGTGCACACCCATGGGTGCCTAGCCAAGGATAGAAAC
    TTGTATCTGATAAGGAAAGAGGATGCTGCAGTGGCCACACTCTGAGATCACCTCCTGCCAAATTATACTA
    GAGTGTTTTACATAGTCTTGAAAACACTAGGTCAAATATGTTGTCATCCAGATATGAAAACTCTGTGCAA
    CAATTCAGAAATACAGTGGTCAGGACAACTGGTATGTAACACTTTAGTTCCAGCCCACATTAATCTCACA
    TCTTTTCTGTGGTTTCAATAAAGAGCACACATGTTTGGAACACCATCTCCACTTTGTATGCTTATCCTTA
    TGCATCAAACTTTTCCTGTAATTTCCTACCCCGCACAGGTTCCTGTCTTGATCTCTTTTTCTAATGAACA
    GCAATACAGAAGTGTTGGCCAAATGAACACTTTCACCCCAAGTTGCTTTGCCATTGTGTTTCATCACAGC
    ATTAGTAACTCCCAGTAAGGCTACTGGTTACCCTGCATCTTCTATGTAGATCTTTTGATGAAGTTCCAGG
    CTTGGGGTCTTTATCTGACTGTTATCCTGGTTAATTCATGTCCACCAATAGAATATTGTTCTCATTTTCA
    ATATCATATGAAGTTACCTGTTTATAGGATCTTCCTAAAGCAGAAAACTATATAAAATGTCTGCTTACTT
    TAAGAAAAGTATGTGTCCTTGGAGGTAAATGGAGGAAAGGGTGGAGGATGTTGAGTAATGGAAGACTGGC
    TAATACAGGAAGGTCACAGAATTGAATGATTTTAAAAATTTTAACTCCTCATCAATGAGGTACTTCAAGT
    TGAGGCAGGAGTCCTTGATGCACAGGTGACCCAAAGGCCCCAGCCTCTGTTTCTTGGTCTGCTCCAGTCT
    CCCGGCTCAGCACAGTTCACTGAGTGACAATCTTTAAGATAGTCTTTCAGGATACAGTTATCACAGTTTT
    CAAACTCTCTTCATTGAAACAATATAATGAGTCAGAGTCCAGTGTGCCATTAATAGGCCCTATGCAATAG
    GATTTTACTTCATCTGTGGAAAGAAACCACCATGGCCTCATCAAGGCCTCATTTGATGATTAGTGTAGAA
    AGCGTCCCCAGAGCTTTGCTGGGATGAAAACCCTGGCAAGATGTTTAGGGCACTCTCCATCTGACAGGAC
    AATTCTATCAAGGGTTGCTTCCATATAGAGAGAAATCTCCACATCTGCAGTATTTCCCGATTTATCAACA
    GTTCTTTACCCCGTGTCATATGCATAAAATCTTTTCTCTGTAGAATTTTCAGTACTAAAAACTAACAAGG
    ATGTTGGTCCTGATATCAGACATAATAAATAAATAAACATCAAATTATACCCTAAACATGTGGAGATGGT
    TTTCTGTTATGAATTTATTGGCTCTCTAAAAAGTGTTAATTAAGCCAGGCGTGATGGCACATGCCTTTAA
    TCCCAGCACTTGTGAGGCAGAGGCAGGCGAATTTCTGAGTTTGAGGCCAAACTGATCTACAGAGTGATTT
    CCAGGACAGCCAGGGTTACACAAAAAAACCCTGTCTCCAAAAAGTAACAAAAAGAAAGTGTTAATTAACA
    TCTACACTTTAAGATAATTTGGTGGCAAAGGTTAATAGTCTGAAATACTAGATATGAAAGTATGACACCT
    AAATTGCATGCAGAGAATAAAGCTGAATTCCAATGAGATTCATGCCTTGTGAATCCATTCCAATCTGATC
    TCAATCTTCAAACATGTTTGTGCATAATTTACATCTTAATCAGTTGCTGGAAATTAAAAGGACATAAGCT
    AAACTTAAAACTCTTTCTATTTAATGTGTCAGAATAGAATATGTGCACTGAAGTTTTCATGTGCATAGGA
    TATCATTGTTACAATGATGGTTCAAATACGCACCAGTAGCACAGGTGATGCTTGACATGAAAAAAACTGT
    GACCAGAGCCCAGACGTTGATGTTGGCTGAAAGAGCCTAGTGTCTCACATTTGATCAAGCAAAGTGTTAT
    TCAGAGAAGCAGTGCCAGATTTGGGATCCTTCTTAATGGATCAAGAACATGAGGAAGATTTGGAAGCCAG
    ATTGATGAGATTACTAGAATCCTGGATCTGAACACACAACACACAATAGTAAGTTGAACTTTTCCACGCA
    ATGCTAAAGATAAAGCATCCAGTATCATGTTATACAGGACCAAGGTGAGGATCAGTCTGTGGGTGAAGTA
    CAATGAACTGGAAATTGTTTGGATTTTAAATGTTGGTTTTTAAATTATATATAAAATATATATATATATA
    TATATATATACATATATATATATATATATATATATATATATATATCGGAACCAACATTTAAAATTTGGAT
    TTTAAATGTTGGTTTTTAAATTATATATAAATTATATATATATATATATATATATATATATATATATATA
    TATATATATATATATCGGAACCAACATTTAAATTCCTAATTCTTAAGGACTTCACTTTTGACCAAAAATA
    TTTGAAATGGGTTATTTAGGTCTGTGGTGGTTTGAATATGCATAGCCTATAGGAAGTGGAAGTATGGCCA
    TTTTGTAGTATGTGTAGCCTTGATGGAGGAAGTACATCACTATATGGTGTTGTGAGAGTTGAGATCCTAT
    GTTCAAGTTCTGCCAAAAACAGAAGAGAGTCCCCTCCTGGATATTTGAAACAGATGCAGAGGCCCAAAGC
    CAAACATTGGGTATATCTCAGGGTTTCTTATGGAAAAGTTGGCTGAAGGATTGAAGGCCTTAAAGGGGAT
    AGGAACTTCACAGGAAAACCAACAGATTCATCTAACCTAGACTCTAGGGGTCTTTCAAAGGTTGAGTCAC
    CATACAAAAAGGACACAATGGCTAGACCTAGGTCCCTGATACATATGTAGCAAATGTGCAGCTTAGACTC
    CATGTGGATTCCCCAACGACTAGAGCAGGTATTGTCCCTGAAGTTATTGCTTGTCTGTAGAATACATTTC
    CCAACATAATTGTCTTGTCTGGCCTCAGTAGGAGAGTATGTTCCAATCCTGGAGAGACTTGATATGCCAG
    GATTGAGAGATTAAGGGTCTCCCACCATCTCAAAGTTCATGGGTATGACAGGGGAGGGGCAGTGCAGGTT
    TTCCCCATCTCTGATTTCCAGCATTTGCACCCCCAATATTGAGGGGGAGGTCTAGCAATTGGAGGGGGGA
    CAAACAGTATGAGAAAGCTAACTTTAGTGGTGTTGTCACAGTGTGGGGTATTGTGGGTGGGAGTGGAGAT
    GAATCCTCCTCCTCCTCAGGAGGCTGTAGCAGGTGCTTGCCCTCTTTTGGGACAGTAGAGCTGTGGTCAG
    TACTGGCCTGTTCCTGACAAATTTATTCTGTGCTGTGACCATTTATTCAAGGGAGGAAGATTTAAGACTT
    GCTATGATAACCTGACGAATCTGGACAAACAAGAGACAGGAGGTAACACCTGAGTTACTCTTTTGCTTGC
    TAGTACAGAAGAGCACTATAATCCACAAATTGGGGTCCCACATATTCTTGAGTGGGATCCAAGGTGCCAT
    AATTTCAGCCACATTCCAAAGTCCCTCAAGGTCTGACAGTTTAGTCTTTAGGCTTCTCCTAACCAAATCA
    TATTTGGAGTTCTTTAACATAAAAGGGTAGTTTCCCCATATCACTGCCAGCAAAACAGGTTGAATTTGGA
    CAGACAAGCAAAACTATCACAAACAAGACAGACTATGTGTGCGATCCAAATGTCTTGTGATTAGAGGGGA
    AGTTCTGCAGCTTATTAGGCTGTGTCCTTATGCCCACAAATGTCTTCAGATAGGAAAGGGCCATTGGGTG
    CCAATCCTTAGTTCTTCTGTTTCCTGGGCTGTCAGTTTTTATGTGGAGAAGACATGAACCAAATGCAAAG
    TCATGTATCCTACAAGAACTGACATACACAGACAAACAAGGAATAACAATGAGCTCTCTCATTCACCTAA
    GGGGGTCTTATAACATAGAACAGAAAGGGGCCAACTTAGCAAGAATTGACCAAAAGGTGGTCACCTAGAC
    CACACCACAATGCAGGAAGGATATCAATGAAGGAAGAACAAAGGAAAGGCCAAATCAAGTTTGTTGGCAC
    ATGACATAAAACAGTGCTCAAAAAACAATAGATGCGAGCAAAATGAAGCATTGGAATCATATCGGGGTAC
    ATAGGGGTCACTCTTACCCCTGTTCAAGTGCCAGATGTTGTTTTAGCCTTAGGCTCCCTGAGTTTGTCTT
    TAGGGGAAATGGGTAAGAATACACAAAAATAATGTCACAGAATCTTAGAGGCAGATGAGAAGTCAAAGCA
    GACTCATTTATTGCTATAGAAAAGAATGCCTTTATACCTTCTGTCCATAACACCTCTGCCCATATATGCT
    CATCTCTGTGAGGCAATGGACTACCTGCAGACAGGCTGGTATCCAGTCAAGCTGAGGTCTGAACCACAAT
    GGTCGTAACTCACCTAAAGGACGTGGTAGGCATGACGCGATAGGCGTTCCCTCATGCTCCTGGAACTCCG
    GCCCCTGCCTAAGGTACCACCTCCCACAGCCCCCACAAGAGAAGCATGGTCAGTAGTCATGTAAGCAATG
    GCCCAAGCTTCTGACCTTCAGCCTAAACTCCTCCCCAGTTACCTAGCAACAGTGAAGACCATAAAATGGG
    ATGTTAGGCCCCCACCTCACTCTCTTACTCCTTTGTTCCTTTACCTCTCACTTCTCTCAATTCTCTCTCC
    TCTTCCCTTTCTTTGTCTTCTTCTTTCCTTGTCTCTCTGTCTTTCTCTTTCTCTCTAGCCTTCTCTGCCT
    CTCTCTCTCTCTCTGTCTCTCTGTCTCTCTCTTCTCTCTTTCCCTTGAATTTCTTTTTTTCTTTTTTCTT
    TTTTTGATGAGCACAGTATAAATAGTTTATTGCATTGTTTCTGAATGTGGCTGTATTCTCTATTGTTCTC
    TTTCTTATTTTTTTTCTTTTTTTGGTTGTTTTTGTTTTTATAGTCTCGCACAGAATTCTACATCTACCAA
    ATCCCCATTGTGTACTTTAGTTTTGTCTTGTATTCAAAGGTTCTTTCAGAAAGAATCTTAAAGATGAAAT
    TTGCCTTCCAACTTTTCAAAAATACATATAAAGATAGATGTTACATAGTTCACGGAATAGACACATATAC
    GGAGATGCAGCAATATCTCCTTTGTGCCTCTTGTATATTCATGTTATTTCCTCAACTAAAAATACATAGC
    CACAAAGACATACAATGAGCACTCCACTTAGGAAAATATGGCCATATTTTTTTACATTTTTATGATTTTA
    TGATTAGGTATATTCTTCATTTACATTTCCAATGCTACCCCAAAAGTCCCCCAACCCTTCCCTCACTCCC
    CTTCCCCACTCCCACTTGTTGGCCCTGGAGTTCCCCTGTACTGAGGCATATAAAGTTTGCAAGACCAATG
    GGCCTCTCTTTCCACTGATGGCCCACAAGGTCATCTTCTGATACATATGCAGCTAGATACATATACATAC
    ACGAGCTCCAGGGGGTACTGGTTAGTTCATATTGTTGTTCCACCTATAGGGTTGCAGATCCCTTCAGCTC
    CTTGGGTACTTTCTCTAGCTCCTCCATTGAGGGCCCTGTGATCCATCCAATAGCTGACTGTGAGCATCCA
    CTTCTGTGTTTGCTAGGCCCCATTATAGCCTTGCAAGACAGCTATATCAGGGTCCTTTCAGCAAAATCTT
    GCTAGTGTGTGCAATGGTGTCAGCATTTGGGGGCTGATTATGGCATGGATCCCCGGATATGGCAGTCTCT
    AGATGGTCCATCCTTTCATCTCAGCTCCAATCTTTGTCTCTGTAACTCTTTCCATGGGTGTTTTGTTCCC
    AATTCTAAGAAGGAGCAAAGTGTCCACACATTTGTATTCATTACTCTTGAGTTTCATGTGTTTCCCTTGC
    ATTTCTATAATAAACCATAAGGAGTCTCTGCTCTACCAAGACCCGCTGCACACTCTGGTCAGTGTTGGGA
    ACTTTTCCCCTATTCCCTCTCTCCTATAACTCCGGGGCTACAGGGTGTCTCCTTTGGGTCCCGGTTGGGA
    GCTGTCTCTTCTCAACCCCCTGACTCATGGGTCAGAGGCCTAAATCTCCACCCAAGGCTGTGTGAAAAGC
    ACCGGGTGGTCTCCCCATATCTCCCTGTCCAGAGCACAGGAACTCTGGCCGGACATGGCATATTTTTCCT
    CCCCAACTTCTTCCCCGGCCTCCTCAGGGCTGTCCCTTCATTTTGTTCCCCACACATCTCCACATGGCTG
    CCACCATCCAATTGGCTGCTGAGGTCACACACTCTGTCTTTGTTCTTCTCTGAGTCTCATGCAGGTTTTG
    TGTTAGTAAATGCAAAAGTGCCTGCTGTGCATGCATGAACCATTACAGGCTGCTAGGCAGAACATGCTGA
    CTTGCTCCTGGATTATAAATCCATCACTGTGATAGCAGGACATATCCAGAAGACATTATTTAACAACACT
    CCTCTTCGTGCTCAACCTCTCATGGTCTTTCTACCTCCTCTTTCTTAGTGTTCTCTGAGCCTACATGAAA
    TGTGAACAAACCTGAAAAAAATCTCTGTGTCAAATACATAGTGTGGATTGGGAAGGAAAAACCCTGCACT
    TGTGTGTGGGCAGGGAAATGCTGGTGCTTTAACAGGACAAGTGCGGTGTGGCTAGAGAAAGTGATGAGAA
    GAAGGGAAGCATGAGAACTGGGTGGGTGGATCCCATGTCTACTGAAAATGCTATGTTGATGTCAAGATAT
    TGTGTCTTGTTACAAAAATTCATTGAGTACCTAGGTTATTCTCAGTATATAAAAGGGGAGGAATGAAACT
    AGAATTAAACACACACACACACACACACACACACACACACAAACACACACACACGAGTAGAGAAAAGAAA
    TAGTCATGAGTTGCCTAGTGAATGAAGAGCGGAAAATGGTGCAGTTAATAGGGATCATAGAAAGAACTGG
    GGGATGCACACGAATGGGTTTCCTGTAATTATGTCTTCATAGTAATCTCTGCTCAATAATCAGACAGTGA
    CAATGTATGCCTCATTTACAAGCCCTGATGGCCTCTCAGAGGAAAGCATCTCTCTGAAATGAATAAAGTT
    CAGAAATGTCCTAAGTGTCCCTGTCACAGGAAAGCAGTGTTGGTAACGTTTCCAGGAAGCTCAGTCTTTG
    TCAAATATCCACAACAAGAAGAAGCCATGTCTAGACAGACAACAGACTGGGAAAGACTGAGCTCATGTAT
    GGAAACACAACTATGTGTCATGCTTTTATTTTCACATTATACTGAGGGGATATGACATTATAGAAACACA
    GTTTGTTCTTTGCATATGCTGAGAGAGGAACTAGATGAAGTGTGCTAATTCTTAGCAATAAAAAGATATA
    CAAAGTGGTACTTTACTGTTTCAATTTTTGTAACTGGCATCATTGTCTTTGATATTTTATATCTTCCTTG
    AGCACTGCCTTCTCTCAAGTGTCCAACTTCAGAGTATGCTATAGCAGGAAGACTACCAAATAAGATTAAT
    TTTTTTGTACCCATGAAAAAATTATGTGCCCTGACCCCTGTTCTCTGAAAGAGGAGCCAAGTTCTGGATT
    CCCAGATCCTCATATTCATTGATCAGCAGTGAACACAGATCATTCACCATGGACATGGGGCTCATCTGGA
    TTCTCCTTATTGTTTTTAAAAAAGGATTTCATTGGGAAAAGCTGCCTCATATTTCTATGACCAGGAGAGG
    AAGATACAGCTAGAGACACAAGCCCCACCATGTAAAATCTGTATGGTACTCTCGTTTTCATTTTACAACA
    TTTTGCTTTTGCATTGCAAAGGAGCAATAAGGGTTCAGCAATCAGCACTGTAACTGTACTTTTAAAATTT
    CCACCTCTACCCTCTGTGTCCTCTATCTAGTGATAGAAAGTGAAATAAGCACATAAAGCATGGGACAAGA
    AGAACACACAGAGGAGCAGAGACTGGCTACAAGTGGCAGCCAGCATGGAGCTGGACAGAATTTAAAAAGA
    TAAAGAGAAATGTCATGGCATGAAGCAGTGACTTTTTCTGTTCACAATGCCTGCAAAAACTTTATGGAGC
    CTACTACTGCTGAGATATGCAGGTTTGGTTCCAGAGAGGATTTTCTGTTTTATTTAATTTGCTTTTAAAT
    TTTTCTTCTTTGTATAGTCTGTATTTTTAAAAAGGGGTTGAATGAATACCTAAGCAGTTGGAAAATTTGT
    GAGTAGAAACCGAGGGCCTGAGAAACAAATAAATCAAAATTTTGAAATGGCAAAAGAAAGGGTTCATTCT
    ATTTTCTCTTTTCAGAAAAGGTTGCAAAGTTGGATGTGCAAATGGAGATGTTATGGGTGGACTTGGAACA
    TCTTGGGAAGGAAGGAACCCAGGAAAAGAAAGAATGAAATGGCTCAGCCTCAATGACTGAGCAAGAGAGT
    TAGAGTCACCCACAGGAGAAAAGAAGAAAATAAACAGCACTGGGGTGAATTTGGGTCAGAGAAAACCTTA
    AAATGCCAGAGGACAATGTGATGAAAGAGACCATTTGAAAGAAAGGGTTAACCTCATTCCATCAGTCATG
    CCAGAGTTAGAGAATGGGCAGTCTGGAGTTACAAGATCACGATTAGCCTTCCCAGTATGTATACAGCATA
    TTCCTGATAATGAGATGAAGCAAAGTTTGACAAGGTAAGATTGTATCCTATAGTAATATATAGATCAAAG
    GCATGTTGCAGTAAATCTCCAACAGAAATAAGCCCGGGCAATGAAAACACAACTCAATTAATATGAATAC
    GTGCTGTGCACCTAGACTGGGCAGATCTACCACTCCACTACCATATGAGAGATCCCTTATAACTTGTGGT
    TTCTCCAGGCCAGCTGCTTCTGCTCTACTTTCCTTCCTCCTCCTCCTATGTCATCCTCTCCCTCACTCTT
    TCTCTCCCAAAACTTTCAGCTGCACCTTCCCCTCTTCATCCCCCAATCAGTGGCTCTAGCCTTTATTTAT
    AAATTAAGGTAGGAAGAAGGTTTATAGGAAATTACCTGAGTGTTGACGTGTTGATAACCCCACACAAGAG
    AACAAAATTAATATCAAATATGATTAGCTCCAGGGTTATATGCAACAAAGGCATGATAAAGTGGTCATGA
    TTTCATATGAGATGTACTGGACTCATGTGAAAAAACGTTTAAATACATGGGCTTACTCAAAATATAGACT
    CATACCCCCAAGATGGGAAGAGACTGGTAACATTTGTACTGGAGGCTGGTCTGCTGTGGCAGCCATTAAC
    ACAGTGGAGGGAAGAGCCTCAAAGAGTGAAATAGAGGAAGGGGAACAAATACAGTAAACCACCAGTTACT
    ACTTAAAGGGCAGTGTTCTGATGTCCTAGGGAGGGCACTCCAAAATACCAATGGCCTTATCCTTAAATTT
    ATTGTTTAATGAGCCTACACTGATCTCAGTGGCCCACTACTAAGGAGAAATGACAGGCACTTGAACAGCT
    GATATGAGAACAGCTGGAGGCACAGTATACAGAAGAGTTTACAAGCCTATGGAACTCCCCTGTATTTTTT
    TATGATGAGGAAATCTGAAAAATGTAAAATGTTGAAAGATTTAAGAGCAGTTATTAGAGTAGATCAACCA
    ATGAGTCTCTTGCAGCCTGGAATTCTTTTATCTTGTTTGTAACAACAATCAGGCTCCATAAATTATAAAC
    TATAAAAATTTACTTTATAAATTATAAATATATATATATGTGTGTCTGTAGATAGATAGATAGATAAATA
    GATAGATAGATAGATAGATAGATAGATAGATATATGGATTTGATGGTTGCAGCAAATTCTAATTGGTTCC
    AACAACCCTACTCACATAATACATTCATACAGGTTTGATAGATGGAGCTAAGTTTTAAATAAATTATTTT
    TCTCCCATGGCTTATATATACACCACCAAAATTCTCAAAAATTAAAATGTGATTGTGTTGTATTTTTCTT
    TTACTGAATGACTATAAAAAGTTACAACATTCTCCATAAATTTACATGAAAAAATATTATGTAGTGCAGG
    TAAAGAAAACAAATTGACCCAAGAATGGTGTATATTCATTACTAAGCAACTTTTTAGATTCACAAAGTGT
    GGGTAAACAAGGTAATTTTTTCAATCAGTTTTTTTTAACTGGCAGGCAGCAATTCAGAGTTACAATGAGA
    AGATTAATAATTTTATTGTGTATTTTAAAATAAATCTTACAAAAATATTAATAGAATCACAAATTTATAC
    CTTTGTATAAAAACAATCAGTCATTTCTACTTTAAGAAACAGAACTCACATCTACTCATCAATCATTTTA
    TTAAGTCATATTACAAAGCTGAGTGCTAACATGGGTATAAGAAAACCATAACCTTATTCACCAGCCCAGC
    GTCAAAAAGAAAAAAACCAGTCATATCAGCTGCTGCTTCAAGAGTTCTTGTTCCTTGACATTAACAAAAT
    CCCTAGCTTAACTATTAAATTTTTTTTCAAAACTTCTAATTGATCCCTTAGATAAATGTTTGTGCTAACC
    ATCGGGACACATCCCATGAGTTCTGAAGCAGTGTGTTGTTCTTCATGCATGGCCCTTTTGTAGAGCTGTG
    AGTGTAGGGGAAGAGGGGGGAGAGAGAGCCCGTGTCCAGCCAGAGATCCTGTGCTCTGGGCAGGCAGACA
    CGGGAGGACAACGGAACACTTTTCACTCGGCCTTTGGTGGGCATCTGGCTGTGTGAAGTTACTGACCCCA
    CATGGTGGGGGATGGACAAGGGGCAGCCCCTGGTACCAGGAGCCCCAGGGCTACACTCTCGGCCCCAGAT
    ATACAAGAAGAGGGCAGAGGGAGAGAGGCTCCCACACAGGCGAGAGTCCTTAGTCTGGTCTGTGGCTGGA
    GCAGGGGAATTCCTTCTGATTGGAGATTAGGCACAGCTGATTAGGGGAAAGCCTACCCCATCATCCAAGC
    ACAATGGACTTTGAGGAACAGAGCCAGTCTAAGCTTTTATAGCTTTATGGTAGAAAGGCAGGGAGAAAGG
    AGAGAATGTGGAGAGAGACAGAGAGAGACTGGCCATGGCCAAGAGGAGGGAAGGGGGAAGAGAGAGAAAC
    AGGAAAAGCTAGAAAGTAAGATAAGAGAAAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGCAAAGTG
    GGGCCAAGCAGCCCCTTTTCTAGTGAGCTTGTCATCTCACAGTTGCTAGGTAACTGGGGAGGAGTTTAGT
    CTGAAGGTCAGAAGCTTGGGACCTTGTGTATGTGACTACTAACCACAGCTTCTCCTGTCGGGACTGTGGG
    AGCAGTAACTTTGACAGGAGACAGGGATCCAGGAGACATGAGGGAACACCTTCTGTCCCACATAGGTGGA
    ATCGGTTGTACCAGGGTTCAGAACTCAACTCCACTGGAGACCAGCCTATGTGTGCATAGCCCATTGCCCT
    ACAGCCTTTGACATTCTACAGAGTTCTGAGACTGGTAGAGATACAAAATAGCTAGGATTACACAGAGAAA
    CACTGGCTTGACAATAAAACTTCCAAAACAAATATAAATGAATAAATACACAAATTGGAGCAAGTGAACT
    TGCACTAAATCCATCAAAACTTGCACAGGATGGCTGTCTCCATAATGTTCAGATCTACTTCTATTAATGT
    CATTAAGAAGACAAAGATTATGCACAAAAAGAAACAAAACAAGAAACCCAAAAGGTAAAGGCTCCAATTG
    TAAGTAATAGACCCACAGTCTCTGAGGCCTGACTGTGCAGGTCCTCACCTTTGGTAATCAGCACTGAATG
    CAGACCACTCCTCATGGACTTTGGGCTCAGGTTTGTTTTCCTTGTCCTTATTTTAAAAGGTAATTCATAG
    AAATGAGATCCTGCCAGTATTGTGTACATGAGAAATAGAAAAATTGGTTTTCTTTGCTCTATTTTGTTTT
    GTTTGGTTAATGACAGTTTCCAAATCAGCATTCTTTGCTTTGAGGTGCCCAGTGTGAGGTGAAGCTGGTA
    GGGTCAGGGCAGCCTGGAGGGTCCCTGAAACACTCCTGTGCAGCCTCTGTAGTCACTGTGAGTGACTACT
    GAATGACCTGGGTCCTTCAGGCTCTAAAGAAGGGGCTGGAGAGGGTGGAAATAATTTTTAATGGTGGAGG
    TAGCACCTATTATCCAGACACCATGAAGGGCTGATTCACCATCTACAGAGATGATGCCAGAAACACACTT
    TACCTGAAAATAAACAGTCTGAGGTCTGAGTACACAGCCATGTGTGTGTGTGTGTGTGTGTGTGTGTGTG
    TGTGTGTGTGTGTGTGTGTGTGTGAGTGTGTATTCATATATATATATATAGTGTGTATGTATATTCATAT
    ATATATGTATATTCATAAGGTTGAGTAAATGGACTTAAACTGATTCCATCACAACTTCCATGGGATGGAT
    ATTTCCCAGTGTTAAGACCTGTCAACATCACTGTCATTCAGGAGACAATGATTATGCACAACAAAACAAG
    AAACCCAAAAGCAGAGGACTCCAATTACAATAGACCCAGACCCACAGTCTCTGAAGATTGACTGTACAGT
    TCAACCCAGCCCTGTACTTCTCTTCCCTAGAATTTACATTACTGAGTAACTGAGGAAAGCTCTACAATAT
    CTGTTCTCTATAGTGGTCAACACCTCCAAACACAGGTTACCCATATTCATGCCTGCCTTCTGCTACACTT
    CTTGCCATAATGTAGACTACTTCAGCCTATTTTGTACTCCAGTTAACGAAACTCAAGACTAGCTGCATGT
    TAGTCCTTATTCTGAAATATTATGAACAGGTGACCTCCCATCATTCACCAATGCAATAATCATATTTAGG
    AATATGAGGTTTTATGAGATATAAGCACAAGGGAGAGAAAGTAAGAAAACTACATAGATATATAGACTGA
    CATAAATCAAGACTTGCATGAGCTAGTGCCCAAGTACCATGTCCCTAAGTGGCAAGGAGTATCTTTTGAG
    CCTAGTGAGATGAGGTACAAATCGGACTCTTACATCTTTTTAGATAAACATGTGAGATCAATGGACTAAA
    GGCGTGAGCTGGGCTTCCTTGCAATCCATTTTCCATACAAGATAACAATAGATCTGGCTCCACAGACACG
    ATGAGAATAGTCTTAATTAGTTCTTTAAGTAGAATGACTGATCACTAAGAGCCCAATTCCATACTAAATA
    CTCTTCTGGATTATGCACAGATAAAAATTGCACATAGGGCATGGGGCACTGATCTCCCTGCACTACATGA
    ATGGGGGCTCATTTACTAAATGTTCCCATGTTTCTTCCTAGTGCTGCACAGAGCAAATCCTACAACTTCC
    TGCTTGTCTACAATGTAAACTCCAGACAGTACCAGAAAATCATTCCTTATGTTCCTCTCCAGGTGCTTCA
    ACAAGCACAGTGCAAATTTCTGTCACCCTG
  • Molecule Role : Vaximmutor
  • Additional Molecule Role : Vaximmutor
  • Related Vaccine(s): West Nile virus C protein mutant vaccine
IV. Vaccine Information
1. ALVAC-WNV-prM/E
a. Vaccine Ontology ID:
VO_0004731
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Preparation
Three commercially available equine WNV vaccines in horses: (i) an inactivated WNV vaccine (K-WN), (ii) a modified-live vaccine (CP-WN) containing the WNV prM and E proteins expressed by a canarypox vector, (iii) a live-chimera vaccine (WN-FV) containing WNV prM and E proteins expressed in a YF17D vector (Seino et al., 2007).
f. Immunization Route
Intramuscular injection (i.m.)
g. Horse Response
  • Vaccination Protocol: Twenty-four healthy, WNV-seronegative horses of varying ages and genders were placed, in random and blind manner, into three trial groups consisting of eight horses each; two horses in each group received one of the three vaccines being tested (Seino et al., 2007).
  • Vaccine Immune Response Type: VO_0003057
  • Challenge Protocol: The horses were challenged with designated WNV NY99 (Seino et al., 2007).
  • Efficacy: Challenge in horses at between 28 days postvaccination with the chimera vaccine and 56 days postvaccination with the commercial inactivated or modified-live vaccine resulted in 100% survivorship (protection from the onset of WNV encephalitis and viremia). Horses vaccinated with the live-chimera vaccine showed significantly fewer clinical signs than did the control horses and the horses vaccinated with inactivated vaccine (Seino et al., 2007).
2. ALVAC-WNV-PrM/E (dogs and cats)
a. Vaccine Ontology ID:
VO_0004736
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Gene Engineering of PrM
  • Type: Recombinant vector construction
  • Description: A canarypox vector expressing PrM and E genes (Karaca et al., 2005).
  • Detailed Gene Information: Click here.
f. Gene Engineering of E protein
  • Type: Recombinant vector construction
  • Description: A canarypox vector expressing PrM and E genes (Karaca et al., 2005).
  • Detailed Gene Information: Click here.
g. Preparation
Canarypox vector expressing PrM and E genes of West Nile virus (WNV) (ALVAC-WNV) (Karaca et al., 2005).
h. Immunization Route
Intramuscular injection (i.m.)
i. Dog Response
  • Vaccination Protocol: One group of 17 dogs was vaccinated with 10^5.6 TCID 50 (Karaca et al., 2005).
  • Vaccine Immune Response Type: VO_0003057
  • Challenge Protocol: The animals were challenged 120 and 135 days after the second immunization, respectively via the bites of Aedes albopictus mosquitoes infected with WNV (Karaca et al., 2005).
  • Efficacy: The first dose of vaccine induced a detectable antibody response in four dogs and five cats (one immunized with low and four with high doses). After the second dose, all the vaccinated dogs and all of the cats, immunized with high dose had detectable antibody titers, whereas only four of eight cats in the low dose group were seropositive. None of the vaccinated dogs and one vaccinated cat developed viremia following the WNV mosquito-challenge. In contrast, 14 of the 15 control dogs and 9 of the 11 control cats developed viremia (Karaca et al., 2005).
j. Cat Response
  • Vaccination Protocol: Two groups of cats (groups 1 [n=14] vaccinated with 10^7.5 TCID(50) and 2 [n=8] 10^5.6 TCID(50)) were vaccinated twice at 28-day intervals (Karaca et al., 2005).
  • Vaccine Immune Response Type: VO_0003057
  • Challenge Protocol: The animals were challenged 120 and 135 days after the second immunization, respectively via the bites of Aedes albopictus mosquitoes infected with WNV (Karaca et al., 2005).
  • Efficacy: The first dose of vaccine induced a detectable antibody response in four dogs and five cats (one immunized with low and four with high doses). After the second dose, all the vaccinated dogs and all of the cats, immunized with high dose had detectable antibody titers, whereas only four of eight cats in the low dose group were seropositive. None of the vaccinated dogs and one vaccinated cat developed viremia following the WNV mosquito-challenge. In contrast, 14 of the 15 control dogs and 9 of the 11 control cats developed viremia (Karaca et al., 2005).
3. Encephalomyelitis-Influenza-West Nile Virus Eastern & Western, Killed Virus Vaccine (USDA: 13W5.20)
a. Manufacturer:
Wyeth
b. Vaccine Ontology ID:
VO_0002115
c. Type:
Inactivated or "killed" vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
Horse
4. Encephalomyelitis-Rhinopneumonitis-Influenza-West Nile Virus Eastern & Western, Killed Virus, Killed Flavivirus Chimera Vaccine-Tetanus Toxoid (USDA: 4855.R2)
a. Manufacturer:
Intervet Inc.
b. Vaccine Ontology ID:
VO_0002262
c. Type:
Inactivated or "killed" vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
Horse
5. Encephalomyelitis-West Nile Virus Eastern & Western & Venezuelan, Killed Virus Vaccine (USDA: 14W5.23)
a. Manufacturer:
Wyeth
b. Vaccine Ontology ID:
VO_0002128
c. Type:
Inactivated or "killed" vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
Horse
6. Encephalomyelitis-West Nile Virus Eastern & Western & Venezuelan, Killed Virus Vaccine-Tetanus Toxoid (USDA: 48W5.20)
a. Manufacturer:
Boehringer Ingelheim Vetmedica, Inc.
b. Vaccine Ontology ID:
VO_0002284
c. Type:
Inactivated or "killed" vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
Horse
7. Encephalomyelitis-West Nile Virus Eastern & Western & Venezuelan, Killed Virus Vaccine-Tetanus Toxoid (USDA: 48W5.23)
a. Manufacturer:
Wyeth
b. Vaccine Ontology ID:
VO_0002287
c. Type:
Inactivated or "killed" vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
Horse
8. Encephalomyelitis-West Nile Virus Eastern & Western, Killed Virus Vaccine (USDA: 14W5.22)
a. Manufacturer:
Wyeth
b. Vaccine Ontology ID:
VO_0002127
c. Type:
Inactivated or "killed" vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
Horse
9. Encephalomyelitis-West Nile Virus Eastern & Western, Killed Virus Vaccine-Tetanus Toxoid (USDA: 48W5.21)
a. Manufacturer:
Boehringer Ingelheim Vetmedica, Inc.
b. Vaccine Ontology ID:
VO_0002285
c. Type:
Inactivated or "killed" vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
Horse
10. Encephalomyelitis-West Nile Virus Eastern & Western, Killed Virus Vaccine-Tetanus Toxoid (USDA: 48W5.22)
a. Manufacturer:
Wyeth
b. Vaccine Ontology ID:
VO_0002286
c. Type:
Inactivated or "killed" vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
Horse
11. Encephalomyelitis-West Nile Virus Eastern & Western, Killed Virus, Live Canarypox Vector Vaccine (USDA: 14W7.R0)
a. Manufacturer:
Merial, Inc.
b. Vaccine Ontology ID:
VO_0002129
c. Type:
Live, attenuated vaccine; Inactivated or "killed" vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
Horse
12. Encephalomyelitis-West Nile Virus Eastern & Western, Killed Virus, Live Canarypox Vector Vaccine-Tetanus Toxoid (USDA: 48W9.R0)
a. Manufacturer:
Merial, Inc.
b. Vaccine Ontology ID:
VO_0002288
c. Type:
Inactivated or "killed" vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
Horse
13. PreveNile
a. Tradename:
PreveNile
b. Manufacturer:
Intervet
c. Vaccine Ontology ID:
VO_0000947
d. Type:
Live, attenuated vaccine
e. Status:
Licensed
f. Host Species for Licensed Use:
Horse
g. Immunization Route
Intramuscular injection (i.m.)
h. Description
Live flavivirus chimera vaccine(Monath et al., 2001)
14. RECOMBITEKEquine WNV
a. Tradename:
RECOMBITEKEquine WNV
b. Manufacturer:
Merial
c. Vaccine Ontology ID:
VO_0000878
d. Type:
Recombinant vector vaccine
e. Status:
Licensed
f. Host Species for Licensed Use:
Horse
g. Immunization Route
Intramuscular injection (i.m.)
h. Description
Canarypox virus-vectored vaccine(Minke et al., 2004)
15. rMV- WNV
a. Vaccine Ontology ID:
VO_0004712
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Preparation
A recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein (Brandler and Tangy, 2013).
f. Immunization Route
Intramuscular injection (i.m.)
g. Mouse Response
  • Vaccination Protocol: Mice were immunized with varying doses of MVSchw-sEWN (Brandler and Tangy, 2013).
  • Vaccine Immune Response Type: VO_0003057
  • Challenge Protocol: Mice were challenged with doses ranging from 100 to 100,000 focus-forming units of IS98-ST1 WNV (Brandler and Tangy, 2013).
  • Efficacy: A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice as early as two weeks after immunization (Brandler and Tangy, 2013).
16. rWN/DEN4Δ30
a. Type:
Live, attenuated vaccine
b. Status:
Licensed
c. Host Species for Licensed Use:
Human
d. Antigen
PrM and E protein genes of the live attenuated DENV-4 vaccine candidate(Durbin et al., 2013)
e. Vector:
Culex mosquitoes
f. Preparation
All vaccines were diluted to the appropriate titer with safety-tested L-15 medium (placebo). At each vaccination, aliquots of diluted and undiluted vaccine were titrated as described below to ensure potency of the vaccine administered (Durbin et al., 2013).
g. Immunization Route
Intramuscular injection (i.m.)
h . Approved Age for Licensed Use
18-50 years
i. Description
rWN/DEN4Δ30 is a live attenuated chimeric virus vaccine produced using recombinant DNA technology reducing ability to infect replicate nd disseminate in both Culex and Aedes mosquitoes, diminishing its risk of transmission from vaccines to other hosts (Durbin et al., 2013)
17. West Nile virus C protein mutant vaccine
a. Vaccine Ontology ID:
VO_0002998
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of C protein
f. Immunization Route
Intraperitoneal injection (i.p.)
g. Mouse Response
  • Persistence: A C protein mutant is attenuated in mice (Schlick et al., 2010).
  • Efficacy: A C protein mutant protects mice from challenge with wild type West Nile virus (Schlick et al., 2010).
  • Host Gene Response of IgG
    • Gene Response: WNV specific IgG titers were also determined 4 weeks post-challenge. Titers had generally increased to values of 10^4–10^5, with the more pronounced increases observed in mice that had been immunized with lower doses of vaccine strains. All animals inoculated with any of the virus mutants seroconverted, whereas serum samples of animals that had received medium alone showed no WNV specific antibody response. A statistically significant increase in IgG over control mice was observed (Schlick et al., 2010).
    • Detailed Gene Information: Click here.
18. West Nile Virus DNA Vaccine (USDA: 1995.D0)
a. Manufacturer:
Wyeth
b. Vaccine Ontology ID:
VO_0004211
c. Type:
DNA vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
sei whale
19. West Nile virus DNA vaccine pCBWN encoding prM and E
a. Vaccine Ontology ID:
VO_0004415
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse, horse
e. Gene Engineering of E protein
  • Type: DNA vaccine construction
  • Description: Vector pCBINT expressed WNV E protein (Davis et al., 2001).
  • Detailed Gene Information: Click here.
f. Gene Engineering of PrM
  • Type: DNA vaccine construction
  • Description: Vector pCBINT expressed WNV prM protein (Davis et al., 2001).
  • Detailed Gene Information: Click here.
g. Vector:
pCBINT (Davis et al., 2001)
h. Immunization Route
Intramuscular injection (i.m.)
i. Mouse Response
  • Vaccine Immune Response Type: VO_0000286
  • Immune Response: Recombinant plasmid-transformed COS-1 cells expressed and secreted high levels of WN virus prM and E proteins into the culture medium (Davis et al., 2001).
  • Efficacy: The lowest dose tested (0.1 μg of DNA per animal) is sufficient to induce complete protective immunity by our vaccine in mice. It was evident that the presence of WN virus antibody correlated with protective immunity, since all mice immunized with WN virus DNA remained healthy after virus challenge. All control mice developed symptoms of central nervous system infection 4 to 6 days later and died an average of 6.9 and 7.4 days after i.p. or infected-mosquito challenge, respectively (Davis et al., 2001).
20. West Nile Virus Killed Virus Vaccine (USDA: 1995.20)
a. Manufacturer:
Wyeth, Boehringer Ingelheim Vetmedica, Inc.
b. Vaccine Ontology ID:
VO_0001812
c. Type:
Inactivated or "killed" vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
sei whale
21. West Nile Virus Killed Virus Vaccine (USDA: 1995.22)
a. Manufacturer:
Wyeth
b. Vaccine Ontology ID:
VO_0001813
c. Type:
Inactivated or "killed" vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
sei whale
22. West Nile Virus Live Canarypox Vector Vaccine (USDA: 1991.R0)
a. Manufacturer:
Merial, Inc.
b. Vaccine Ontology ID:
VO_0001814
c. Type:
Live vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
sei whale
23. West Nile Virus Live Flavivirus Chimera Vaccine (USDA: 1991.R1)
a. Manufacturer:
Intervet Inc.
b. Vaccine Ontology ID:
VO_0001815
c. Type:
Live vaccine
d. Status:
Licensed
e. Location Licensed:
USA
f. Host Species for Licensed Use:
sei whale
24. West Nile-Innovator DNA
a. Tradename:
West Nile-Innovator DNA
b. Manufacturer:
Fort Dodge
c. Vaccine Ontology ID:
VO_0001140
d. Type:
DNA vaccine
e. Status:
Licensed
f. Host Species for Licensed Use:
Horse
g. Immunization Route
Intramuscular injection (i.m.)
h. Description
DNA vaccine(Davis et al., 2001)
25. WNV recombinant E protein vaccine (WN-80E)
a. Manufacturer:
Hawaii Biotech
b. Type:
Recombinant E subunit vaccine
c. Status:
Licensed
d. Host Species for Licensed Use:
Human
e. Antigen
WNV E protein antigen (Van et al., 2016).
f. Immunization Route
Intramuscular injection (i.m.)
g. Storage
Virus was aliquoted and stored at -80C.
h. Description
WNV recombinant E-protein vaccine (WN-80E) is combined with a synthetic TLR-4 agonist adjuvant. inclusion of a TLR-4 agonist in either a stable oil-in-water emulsion (SE) or aluminum hydroxide (Alum) formulation provides both dose and dosage sparing functions, whereby protection can be induced after a single immunization containing only 100 ng of WN-80E.(Van et al., 2016)
V. References
1. Angenvoort et al., 2014: Angenvoort J, Fischer D, Fast C, Ziegler U, Eiden M, de la Fuente JG, Lierz M, Groschup MH. Limited efficacy of West Nile virus vaccines in large falcons (Falco spp.). Veterinary research. 2014; 45; 41. [PubMed: 24708385].
2. Brandler and Tangy, 2013: Brandler S, Tangy F. Vaccines in development against West Nile virus. Viruses. 2013; 5(10); 2384-2409. [PubMed: 24084235].
3. Davis et al., 2001: Davis BS, Chang GJ, Cropp B, Roehrig JT, Martin DA, Mitchell CJ, Bowen R, Bunning ML. West Nile virus recombinant DNA vaccine protects mouse and horse from virus challenge and expresses in vitro a noninfectious recombinant antigen that can be used in enzyme-linked immunosorbent assays. Journal of virology. 2001; 75(9); 4040-4047. [PubMed: 11287553].
4. Franco et al., 2010: Franco D, Li W, Qing F, Stoyanov CT, Moran T, Rice CM, Ho DD. Evaluation of yellow fever virus 17D strain as a new vector for HIV-1 vaccine development. Vaccine. 2010; 28(35); 5676-5685. [PubMed: 20600494].
5. Karaca et al., 2005: Karaca K, Bowen R, Austgen LE, Teehee M, Siger L, Grosenbaugh D, Loosemore L, Audonnet JC, Nordgren R, Minke JM. Recombinant canarypox vectored West Nile virus (WNV) vaccine protects dogs and cats against a mosquito WNV challenge. Vaccine. 2005; 23(29); 3808-3813. [PubMed: 15893618].
6. Lieberman et al., 2009: Lieberman MM, Nerurkar VR, Luo H, Cropp B, Carrion R Jr, de la Garza M, Coller BA, Clements D, Ogata S, Wong T, Martyak T, Weeks-Levy C. Immunogenicity and protective efficacy of a recombinant subunit West Nile virus vaccine in rhesus monkeys. Clinical and vaccine immunology : CVI. 2009; 16(9); 1332-1337. [PubMed: 19641099].
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