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Hantavirus

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. Hanta_G2
    2. ANDVsSgp1 (Protective antigen)
    3. G1 (Protective antigen)
    4. G1 and G2 (Protective antigen)
    5. Gc (Protective antigen)
    6. HTNVsSgp1 (Protective antigen)
    7. M Segment (Protective antigen)
    8. N protein [Topografov virus] (Protective antigen)
    9. PUUVsSgp1 (Protective antigen)
    10. S nucleocapsid protein from Dobrava-Belgrade virus (Protective antigen)
    11. SNVsSgp1 (Protective antigen)
  3. Vaccine Related Host Genes
    1. Ighg1
    2. Il2
    3. Il4 (interleukin 4)
  4. Vaccine Information
    1. Andes virus vaccine using adenovirus viral vector expressing ANDV NP
    2. Chimaeric HBV core particles carrying Puumala virus nucleocapsid protein fragments
    3. DNA vaccine encoding ANDV glycoproteins
    4. Dobrava-Belgrade virus S nucleocapsid protein vaccine
    5. Hantavirus DNA vaccine pWRG/HTN-M
    6. Puumala virus PUUVsSgp1 (NP) protein vaccine
    7. Recombinant DOBV nucleocapsid protein (rDOBV N)
    8. rVSVΔG-ANDV-GPC
    9. Seoul virus vaccine rCAV-2-Gc
    10. Sin Nombre virus DNA vaccine encoding G1
    11. Sin Nombre virus DNA vaccine encoding SNVsSgp1 (NP)
    12. Topografov virus N protein vaccine
    13. Truncated Recombinant DoBV Nucleocapsid Proteins (Dob-N rNp)
  5. References
I. General Information
1. NCBI Taxonomy ID:
11598
2. Disease:
Hantavirus Pulmonary Syndrome
3. Introduction
Hantaviruses are rodent-borne agents that cause hemorrhagic fever with renal syndrome or hantavirus pulmonary syndrome (HPS) in humans (de et al., 2002). Annually, around 150,000 cases of HFRS are reported worldwide, caused by Hantaan (HTNV) and Seoul (SEOV) hantaviruses in Asia and by Puumala (PUUV), Dobrava (DOBV), and Saaremaa (SAAV) hantaviruses in Europe (Klingstrom et al., 2004). Hantavirus was first identified in the United States in 1993. HPS is a deadly disease from rodents. Although rare, Although rare, the consequences of getting it are serious. Early symptoms include fatigue, fever and muscle aches. There may also be headaches, dizziness, chills, and abdominal problems, such as nausea, vomiting, diarrhea, and abdominal pain. The major HPS symptoms may not appear until the illness becomes life-threatening. Rodent control in and around the home remains the primary strategy for preventing hantavirus infection (CDC Hantaviruses). Hantaviruses can also cause human hemorrhagic fever with renal syndrome (HFRS) (Lednicky, 2003).

Increased numbers of rodents in the household is the strongest risk factor for infection. Among documented U.S. cases of HPS, patients with potential occupational exposures have included grain farmers, an extension livestock specialist, field biologists, and agricultural, mill, construction, utility and feedlot workers (CDC Hantaviruses).

Hantaviruses contain a three-segmented ssRNA-genome of negative polarity encoding four proteins: the nucleocapsid protein (N), the envelope proteins (G1 and G2), and the RNA dependent RNA polymerase (Klingstrom et al., 2004).
4. Microbial Pathogenesis
Rodents (primarily deer mice) carry hantaviruses that cause hantavirus pulmonary syndrome in human. Rodents shed the virus in their urine, droppings, and saliva. The virus is mainly transmitted to people when they breathe in air contaminated with the virus. Functional impairment of vascular endothelium is central to the pathogenesis of HPS, and a myocardial depressant may contribute significantly to the mortality of this disease. Hantaviruses can infect endothelial cells, macrophages and dendritic cells. The mechanism of inflammatory cell recruitment in the lungs of HPS patients may result from specific attraction and adherence of a selective population of inflammatory cells to an activated pulmonary microvascular endothelium (CDC Hantaviruses).
5. Host Ranges and Animal Models
n the US, primarily deer mice, along with cotton rats and rice rats in the southeastern states and the white-footed mouse in the Northeast, carry hantaviruses that cause hantavirus pulmonary syndrome (CDC Hantaviruses).
6. Host Protective Immunity
Klingström et al. reported that the strong Th2-type of immune response induced by Alum against rDOBV N did not induce protection in mice (Klingstrom et al., 2004).
1. ANDVsSgp1
  • Gene Name : ANDVsSgp1
  • Sequence Strain (Species/Organism) : Andes virus
  • VO ID : VO_0011092
  • NCBI Gene ID : 991232
  • NCBI Protein GI : 19744950
  • Locus Tag : ANDVsSgp1
  • Genbank Accession : AF004660
  • Protein Accession : NP_604471
  • Taxonomy ID : 46607
  • Segment No : Segment S
  • Gene Starting Position : 42
  • Gene Ending Position : 1328
  • Gene Strand (Orientation) : +
  • Protein Name : nucleocapsid protein
  • Protein pI : 7.18
  • Protein Weight : 45461.89
  • Protein Length : 428
  • DNA Sequence : Show Sequence
    >gi|19744949:42-1328 Andes virus segment S, complete sequence
    AATGAGCACCCTCCAAGAATTGCAGGAAAACATCACAGCACACGAACAACAGCTCGTGACTGCTCGGCAA
    AAGCTTAAGGATGCCGAGAAGGCAGTGGAGGTGGACCCGGATGACGTTAACAAGAGCACACTACAAAGTA
    GACGGGCAGCTGTGTCTACATTGGAGACCAAACTCGGAGAACTTAAGAGGCAACTTGCAGATTTGGTGGC
    AGCTCAAAAATTGGCTACAAAACCAGTTGATCCAACAGGGCTTGAGCCTGATGATCATCTAAAGGAAAAA
    TCATCTCTGAGATATGGGAATGTCCTGGATGTTAATTCAATTGATTTGGAAGAACCGAGTGGACAGACTG
    CTGATTGGAAGGCTATAGGAGCATACATCTTAGGGTTTGCAATTCCGATCATCCTAAAGGCCTTATACAT
    GCTGTCAACCCGTGGGAGACAAACTGTGAAAGACAACAAAGGGACCAGGATAAGGTTTAAGGATGATTCT
    TCCTTTGAAGAAGTCAATGGGATACGTAAACCAAAACACCTTTACGTCTCAATGCCAACTGCACAGTCCA
    CTATGAAGGCTGAAGAAATCACGCCAGGACGATTTAGGACAATTGCTTGTGGCCTTTTTCCAGCACAGGT
    CAAAGCCCGAAATATAATAAGTCCTGTAATGGGAGTAATTGGATTTGGCTTCTTTGTAAAGGATTGGATG
    GATCGGATAGAAGAGTTTCTGGCTGCAGAGTGTCCATTCTTACCTAAGCCAAAGGTCGCCTCAGAAGCCT
    TCATGTCTACCAATAAGATGTATTTTCTGAACAGACAGAGACAAGTCAATGAATCTAAGGTTCAAGATAT
    TATCGATTTGATAGACCATGCTGAGACCGAGTCTGCTACCTTGTTTACAGAGATTGCAACACCCCATTCA
    GTCTGGGTGTTTGCATGTGCACCTGACCGGTGCCCTCCAACTGCATTGTATGTTGCAGGGGTACCGGAAC
    TTGGTGCATTTTTTTCTATCCTTCAGGACATGCGTAATACCATCATGGCATCTAAATCTGTAGGGACTGC
    AGAAGAGAAGCTAAAGAAAAAATCTGCCTTCTACCAATCATACCTAAGAAGGACACAATCTATGGGAATC
    CAACTGGACCAGAAGATCATAATCCTTTACATGCTATCATGGGGTAAAGAAGCTGTGAATCACTTCCATC
    TTGGTGATGATATGGACCCTGAACTCAGGCAGCTAGCACAATCTCTGATCGATACTAAGGTGAAGGAGAT
    CTCCAACCAAGAGCCACTTAAGTTGTA
  • Protein Sequence : Show Sequence
    >gi|19744950|ref|NP_604471.1| nucleocapsid protein [Andes virus]
    MSTLQELQENITAHEQQLVTARQKLKDAEKAVEVDPDDVNKSTLQSRRAAVSTLETKLGELKRQLADLVA
    AQKLATKPVDPTGLEPDDHLKEKSSLRYGNVLDVNSIDLEEPSGQTADWKAIGAYILGFAIPIILKALYM
    LSTRGRQTVKDNKGTRIRFKDDSSFEEVNGIRKPKHLYVSMPTAQSTMKAEEITPGRFRTIACGLFPAQV
    KARNIISPVMGVIGFGFFVKDWMDRIEEFLAAECPFLPKPKVASEAFMSTNKMYFLNRQRQVNESKVQDI
    IDLIDHAETESATLFTEIATPHSVWVFACAPDRCPPTALYVAGVPELGAFFSILQDMRNTIMASKSVGTA
    EEKLKKKSAFYQSYLRRTQSMGIQLDQKIIILYMLSWGKEAVNHFHLGDDMDPELRQLAQSLIDTKVKEI
    SNQEPLKL
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Nonreplicating adenovirus (Ad) vectors that express Andes hantavirus (ANDV) nucleocapsid protein (AdN, ANDVsSgp1) or glycoproteins (AdG(N) and AdG(C)) were constructed . When administered once, all three Ad vectors, individually or in combination, elicited a robust immune response that protected Syrian hamsters from a lethal ANDV infection that mimics the pulmonary disease seen in humans. No vaccinated animal died, and there were no obvious clinical signs of disease (Safronetz et al., 2009).
  • Related Vaccine(s): Andes virus vaccine using adenovirus viral vector expressing ANDV NP , rVSVΔG-ANDV-GPC
2. G1
  • Gene Name : G1
  • Sequence Strain (Species/Organism) : Sin Nombre virus
  • VO ID : VO_0011086
  • NCBI Protein GI : 1113859
  • 3D structure: PDB ID : 2K9H
  • Other Database IDs : CDD:144967
  • Taxonomy ID : 37705
  • Gene Strand (Orientation) : ?
  • Protein Name : envelope glycoprotein G1
  • Protein Length : 91
  • Protein Note : SNV
  • Protein Sequence : Show Sequence
    >gi|1113859|gb|AAC54579.1| envelope glycoprotein G1 [Sin Nombre virus]
    FLVVLTTATAGLTRNLYELKIECPHTVGLGQGYVTGSVETTPVLFSQVADLKIESSCNFDLHVPATTTQK
    YNQVDWTKKSSTTENTNAGAS
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Study used a deer mouse infection model to test the protective efficacy of genetic vaccine candidates for Sin Nombre (SN) virus that were known to provoke immunological responses in BALB/c mice. Protective epitopes were localized in each of four overlapping cDNA fragments that encoded portions of the SN virus G1 glycoprotein antigen; the nucleocapsid gene also was protective (Bharadwaj et al., 2002).
  • Related Vaccine(s): Sin Nombre virus DNA vaccine encoding G1
3. G1 and G2
  • Gene Name : G1 and G2
  • Sequence Strain (Species/Organism) : Hantaan virus 76-118
  • NCBI Protein GI : 138339
  • Other Database IDs : CDD:190042
    CDD:119058
    CDD:144961
  • Taxonomy ID : 11602
  • Gene Strand (Orientation) : ?
  • Protein Name : Envelope glycoprotein
  • Protein Length : 1135
  • Protein Note : M polyprotein
  • Protein Sequence : Show Sequence
    >gi|138339|sp|P08668.1|GP_HANTV RecName: Full=Envelope glycoprotein; Short=GP; AltName: Full=M polyprotein; Contains: RecName: Full=Glycoprotein G1; Contains: RecName: Full=Glycoprotein G2; Flags: Precursor
    MGIWKWLVMASLVWPVLTLRNVYDMKIECPHTVSFGENSVIGYVELPPVPLADTAQMVPESSCNMDNHQS
    LNTITKYTQVSWRGKADQSQSSQNSFETVSTEVDLKGTCVLKHKMVEESYRSRKSVTCYDLSCNSTYCKP
    TLYMIVPIHACNMMKSCLIALGPYRVQVVYERSYCMTGVLIEGKCFVPDQSVVSIIKHGIFDIASVHIVC
    FFVAVKGNTYKIFEQVKKSFESTCNDTENKVQGYYICIVGGNSAPIYVPTLDDFRSMEAFTGIFRSPHGE
    DHDLAGEEIASYSIVGPANAKVPHSASSDTLSLIAYSGIPSYSSLSILTSSTEAKHVFSPGLFPKLNHTN
    CDKSAIPLIWTGMIDLPGYYEAVHPCTVFCVLSGPGASCEAFSEGGIFNITSPMCLVSKQNRFRLTEQQV
    NFVCQRVDMDIVVYCNGQRKVILTKTLVIGQCIYTITSLFSLLPGVAHSIAVELCVPGFHGWATAALLVT
    FCFGWVLIPAITFIILTVLKFIANIFHTSNQENRLKSVLRKIKEEFEKTKGSMVCDVCKYECETYKELKA
    HGVSCPQSQCPYCFTHCEPTEAAFQAHYKVCQVTHRFRDDLKKTVTPQNFTPGCYRTLNLFRYKSRCYIF
    TMWIFLLVLESILWAASASETPLTPVWNDNAHGVGSVPMHTDLELDFSLTSSSKYTYRRKLTNPLEEAQS
    IDLHIEIEEQTIGVDVHALGHWFDGRLNLKTSFHCYGACTKYEYPWHTAKCHYERDYQYETSWGCNPSDC
    PGVGTGCTACGLYLDQLKPVGSAYKIITIRYSRRVCVQFGEENLCKIIDMNDCFVSRHVKVCIIGTVSKF
    SQGDTLLFFGPLEGGGLIFKHWCTSTCQFGDPGDIMSPRDKGFLCPEFPGSFRKKCNFATTPICEYDGNM
    VSGYKKVMATIDSFQSFNTSTMHFTDERIEWKDPDGMLRDHINILVTKDIDFDNLGENPCKIGLQTSSIE
    GAWGSGVGFTLTCLVSLTECPTFLTSIKACDKAICYGAESVTLTRGQNTVKVSGKGGHSGSTFRCCHGED
    CSQIGLHAAAPHLDKVNGISEIENSKVYDDGAPQCGIKCWFVKSGEWISGIFSGNWIVLIVLCVFLLFSL
    VLLSILCPVRKHKKS
  • Molecule Role : Protective antigen
  • Related Vaccine(s): Hantavirus DNA vaccine pWRG/HTN-M
4. Gc
  • Gene Name : Gc
  • Sequence Strain (Species/Organism) : Seoul virus
  • VO ID : VO_0011085
  • NCBI Protein GI : 284157806
  • Other Database IDs : CDD:144961
  • Taxonomy ID : 11608
  • Gene Strand (Orientation) : ?
  • Protein Name : Gc glycoprotein
  • Protein Length : 106
  • Protein Note : Hantavirus glycoprotein G2; pfam01561
  • Protein Sequence : Show Sequence
    >gi|284157806|gb|ADB80030.1| Gc glycoprotein [Seoul virus]
    VPLWTDNAHGVGSVPMHTDLELDFSLPSSSKYTYKRHLTNPVNDQQSVSLHIEIESQGIGADVHHLGHWY
    DARLNLKTSFHCYGACTKYQYPWHTAKCHFEKDYEY
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Seoul virus (SEOV) is one of the four known hantaviruses causing hemorrhagic fever with renal syndrome (HFRS). A replication-competent recombinant canine adenovirus type 2 expressing the Gc protein of SEOV (rCAV-2-Gc) in BALB/c mice induced complete protection against a intensive infectious challenge with ~1,000 50% infective doses (ID50) for SEOV strain CC-2 (Yuan et al., 2010).
  • Related Vaccine(s): Seoul virus vaccine rCAV-2-Gc
5. Hanta_G2
  • Gene Name : Hanta_G2
  • Sequence Strain (Species/Organism) : Andes virus Case T isolate
  • NCBI Nucleotide GI : 2801763
  • NCBI Protein GI : 2801763
  • Genbank Accession : AAB97456
  • Other Database IDs : Accession:AAB97456; GI:2801763
  • Gene Strand (Orientation) : ?
  • Protein Name : Andes Hantavirus M segment polyprotein
  • DNA Sequence : Show Sequence
    >gi|2801762|gb|AF042137.1|AF042137 Andes virus Case T M segment polyprotein gene, partial cds
    AAGGAAATACCATTTCTGGATATAAAAGAATGATGGCAACAAAAGATTCATTCCAATCGTTTAACTTAAC
    AGAACCTCACATCACAGCAAATAAGCTTGAATGGATTGACCCAGATGGAAATACAAGAGACCATGTAAAT
    CTTGTCTTAAATAGAGATGTTTCATTT
  • Protein Sequence : Show Sequence
    >gi|2801763|gb|AAB97456.1| M segment polyprotein [Andes virus]
    GNTISGYKRMMATKDSFQSFNLTEPHITANKLEWIDPDGNTRDHVNLVLNRDVSF
  • Related Vaccine(s): DNA vaccine encoding ANDV glycoproteins
6. HTNVsSgp1
  • Gene Name : HTNVsSgp1
  • Sequence Strain (Species/Organism) : Hantaan virus
  • VO ID : VO_0011091
  • NCBI Gene ID : 2943078
  • NCBI Protein GI : 38371711
  • Locus Tag : HTNVsSgp1
  • Genbank Accession : M14626
  • Protein Accession : NP_941977
  • Taxonomy ID : 11599
  • Segment No : segment S
  • Gene Starting Position : 36
  • Gene Ending Position : 1325
  • Gene Strand (Orientation) : +
  • Protein Name : hypothetical protein
  • Protein pI : 7.11
  • Protein Weight : 45859.21
  • Protein Length : 429
  • DNA Sequence : Show Sequence
    >gi|38371710:36-1325 Hantaan virus, complete genome
    GATGGCAACTATGGAGGAATTACAGAGGGAAATCAATGCCCATGAGGGTCAATTAGTGATAGCCAGGCAG
    AAGGTGAGGGATGCAGAAAAACAGTATGAAAAGGATCCAGATGAGTTGAACAAGAGAACATTAACTGACC
    GAGAGGGCGTTGCAGTATCTATCCAGGCAAAAATTGATGAGTTAAAAAGGCAACTGGCAGATAGGATTGC
    AACTGGGAAAAACCTTGGGAAGGAACAAGATCCAACAGGGGTGGAGCCTGGAGACCATCTGAAAGAGAGG
    TCAATGCTCAGTTATGGTAATGTGCTGGATTTAAACCATTTGGATATTGATGAACCTACAGGACAGACAG
    CAGACTGGCTGAGCATCATCGTCTATCTTACATCCTTTGTCGTCCCGATACTTCTGAAAGCTCTGTATAT
    GTTGACAACAAGGGGGAGGCAAACTACCAAGGATAATAAAGGGACCCGGATTCGATTTAAGGATGATAGC
    TCGTTCGAGGATGTTAACGGTATCCGGAAACCAAAACATCTTTACGTGTCCTTGCCAAATGCACAGTCAA
    GCATGAAGGCAGAAGAGATTACACCTGGTAGATATAGAACAGCAGTCTGTGGGCTCTACCCTGCACAGAT
    TAAGGCACGGCAGATGATCAGTCCAGTTATGAGTGTAATTGGTTTTCTAGCATTAGCAAAGGACTGGAGT
    GATCGTATCGAACAATGGTTAATTGAACCTTGCAAGCTTCTTCCAGATACAGCAGCAGTTAGCCTCCTTG
    GTGGTCCTGCAACAAACAGGGACTACTTACGGCAGCGGCAAGTGGCATTAGGCAATATGGAGACAAAGGA
    GTCAAAGGCTATACGCCAGCATGCAGAAGCAGCTGGCTGTAGCATGATTGAAGATATTGAGTCACCATCA
    TCAATATGGGTTTTTGCTGGAGCACCAGACCGTTGTCCACCAACATGTTTGTTTATAGCAGGTATTGCTG
    AGCTTGGGGCATTTTTTTCCATCCTGCAGGACATGCGAAATACAATCATGGCATCTAAGACAGTTGGAAC
    ATCTGAGGAGAAGCTACGGAAGAAATCATCATTTTATCAGTCCTACCTCAGAAGGACACAATCAATGGGG
    ATACAACTAGGCCAGAGAATTATTGTGCTCTTCATGGTTGCCTGGGGAAAGGAGGCTGTGGACAACTTCC
    ACTTAGGGGATGATATGGATCCTGAGCTAAGGACACTGGCACAGAGCTTGATTGATGTCAAAGTGAAGGA
    AATCTCCAACCAAGAGCCTTTGAAACTCTA
  • Protein Sequence : Show Sequence
    >gi|38371711|ref|NP_941977.1| hypothetical protein [Hantaan virus]
    MATMEELQREINAHEGQLVIARQKVRDAEKQYEKDPDELNKRTLTDREGVAVSIQAKIDELKRQLADRIA
    TGKNLGKEQDPTGVEPGDHLKERSMLSYGNVLDLNHLDIDEPTGQTADWLSIIVYLTSFVVPILLKALYM
    LTTRGRQTTKDNKGTRIRFKDDSSFEDVNGIRKPKHLYVSLPNAQSSMKAEEITPGRYRTAVCGLYPAQI
    KARQMISPVMSVIGFLALAKDWSDRIEQWLIEPCKLLPDTAAVSLLGGPATNRDYLRQRQVALGNMETKE
    SKAIRQHAEAAGCSMIEDIESPSSIWVFAGAPDRCPPTCLFIAGIAELGAFFSILQDMRNTIMASKTVGT
    SEEKLRKKSSFYQSYLRRTQSMGIQLGQRIIVLFMVAWGKEAVDNFHLGDDMDPELRTLAQSLIDVKVKE
    ISNQEPLKL
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Passive transfer of spleen cells from mice immunized with rNP (HTNVsSgp1) conferred partial protection or prolongation of time to death from fatal Hantaan virus infection in suckling mice which were challenged with Hantaan virus at 40 LD50 (survival rate: 43%) or 4 LD50 (survival rate: 43%) (Yoshimatsu et al., 1993).
7. M Segment
  • Gene Name : M Segment
  • Sequence Strain (Species/Organism) : Hantaan virus
  • VO ID : VO_0011090
  • NCBI Protein GI : 1389703
  • Other Database IDs : CDD:144961
  • Taxonomy ID : 11599
  • Gene Strand (Orientation) : ?
  • Protein Name : M polyprotein
  • Protein Length : 108
  • Protein Note : Hantavirus glycoprotein G2; pfam01561
  • Protein Sequence : Show Sequence
    >gi|1389703|gb|AAB02907.1| M polyprotein [Hantaan virus]
    TPLTPVWNDNAHGVGSVPMHTDLELDFSLTSSSKYTYRRKLTNPLEEAQSVDLHIEIEEQTIGVDVHALG
    HWFDGRLNLKTSFHCYGACTKYDYPWHTAKCHYERDYQ
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Researchers vaccinated hamsters with a vaccinia virus-vectored vaccine expressing the M and the S segments of Hantaan (HTN) virus and challenged them with HTN, Seoul (SEO), or Puumala (PUU) virus. Study found that vaccinated hamsters, challenged with HTN or SEO virus, were neither viremic nor had evidence of virus in their lungs or kidneys (Chu et al., 1995).
8. N protein [Topografov virus]
  • Gene Name : N protein [Topografov virus]
  • Sequence Strain (Species/Organism) : Topografov virus
  • VO ID : VO_0011089
  • NCBI Protein GI : 4757106
  • Other Database IDs : CDD:109884
    GOA:Q9WMG3
    InterPro: IPR002214
    InterPro: IPR010989
    UniProtKB/TrEMBL: Q9WMG3
  • Taxonomy ID : 83192
  • Gene Strand (Orientation) : ?
  • Protein Name : N protein
  • Protein Length : 433
  • Protein Note : Hantavirus nucleocapsid protein; pfam00846
  • Protein Sequence : Show Sequence
    >gi|4757106|emb|CAB42097.1| N protein [Topografov virus]
    MSNLKDIQDEITRYEQQLIVARQKLRDAEKTVEVDPDDVNKNTLQARRQTVSALEDKLADFKRQLADHVS
    RQKMDEKPSDPTGIEPDDHLKERSSLRYGNVLDVNAIDIEEPSGQTADWFTIGVYIVSFTLPIILKALYM
    LSTRGRQTVKENKGTRIRFKDDSSFEDVNGIRRPKHLYVSMPTAQSTMKAEELTPGRFRTIVCGLFPAQI
    QARNIMSPVMGVIGFSFFVKDWPERIKNFLESKCPFIKPEVKPGAPAGEADFLSRNQIYFMRRQEVLEDN
    HIPDIDKLLEYASSGDPTAPDSIESPYAPWVFACAPDRCPPTCIYIAGMAELGAFFSILQDMRNTIMASK
    TVGTAEEKLKKKSSFYQSYLRRTQSMGIQLDQRIILLYMVEWGKEMVDHFHLGDDMDPDLRNLAQSLIDQ
    KVKEISNQEPLKI
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : To investigate the ability of recombinant N (rN, nucleocapsid proteins) from different hantaviruses to elicit cross-protection, we immunized bank voles with rN from Puumala (PUUV), Topografov (TOPV), Andes (ANDV), and Dobrava (DOBV) viruses and subsequently challenged them with PUUV. All animals immunized with PUUV and TOPV rN were completely protected (de Carvalho Nicacio et al., 2002).
  • Related Vaccine(s): Topografov virus N protein vaccine
9. PUUVsSgp1
  • Gene Name : PUUVsSgp1
  • Sequence Strain (Species/Organism) : Puumala virus
  • VO ID : VO_0011088
  • NCBI Gene ID : 2943083
  • NCBI Protein GI : 38371721
  • Locus Tag : PUUVsSgp1
  • Genbank Accession : X61035
  • Protein Accession : NP_941984
  • Taxonomy ID : 11604
  • Gene Starting Position : 42
  • Gene Ending Position : 1343
  • Gene Strand (Orientation) : +
  • Protein Name : nucleocapsid protein
  • Protein pI : 6.05
  • Protein Weight : 46970.43
  • Protein Length : 433
  • DNA Sequence : Show Sequence
    >gi|38371720:42-1343 Puumala virus segment S, complete sequence
    AATGAGTGACTTGACAGATATCCAAGAGGATATAACCCGCCATGAACAGCAACTTATTGTTGCCAGACAA
    AAACTTAAGGATGCAGAGAGAGCAGTGGAAGTGGACCCAGATGACGTTAATAAAAACACACTGCAAGCCA
    GGCAACAAACAGTGTCAGCACTGGAGGACAAACTCGCAGACTACAAGAGAAGGATGGCAGATGCTGTGTC
    CAGGAAAAAAATGGATACTAAACCTACTGACCCGACTGGGATTGAACCTGATGACCACCTCAAGGAGAGA
    TCAAGCCTTAGGTATGGAAATGTCCTTGATGTAAATGCAATTGACATTGAAGAACCAAGTGGCCAAACAG
    CAGATTGGTATACAATTGGAGTGTATGTGATAGGGTTCACACTTCCTATCATCCTTAAAGCTTTATACAT
    GCTCTCAACGCGTGGGAGACAGACTGTAAAGGAAAATAAGGGGACACGTATAAGGTTTAAGGATGATACA
    TCATTTGAAGACATCAATGGCATAAGGAGACCAAAGCATTTATATGTTTCTATGCCTACTGCCCAGTCAA
    CTATGAAAGCAGAAGAACTCACACCTGGCAGATTTCGCACAATAGTATGTGGTCTTTTTCCCACTCAGAT
    CCAGGTTCGTAACATCATGAGTCCAGTTATGGGGGTCATTGGTTTTTCATTCTTTGTGAAGGATTGGTCT
    GAGAGAATCAGAGAGTTCATGGAAAAAGAGTGCCCATTCATAAAGCCTGAAGTAAAACCAGGCACACCAG
    CACAGGAGATTGAGATGTTAAAAAGAAATAAGATCTACTTTATGCAGCGCCAGGATGTGCTTGACAAAAA
    TCATGTGGCAGACATTGACAAGTTAATTGACTATGCAGCCTCTGGAGACCCTACATCACCTGACAACATT
    GATTCGCCTAATGCACCATGGGTCTTTGCATGTGCACCAGACCGATGCCCACCAACATGTATCTATGTTG
    CAGGGATGGCAGAGCTTGGGGCCTTTTTTTCAATATTGCAGGACATGAGAAACACAATAATGGCATCTAA
    GACTGTTGGCACAGCAGAAGAGAAATTAAAGAAAAAGTCTTCCTTTTACCAATCTTACCTGCGTCGAACT
    CAATCAATGGGAATTCAGCTTGATCAAAGAATTATCCTCTTGTTTATGTTGGAATGGGGCAAAGAGATGG
    TAGATCACTTCCATCTTGGTGATGATATGGATCCAGAGCTCAGAGGTCTTGCACAGGCACTGATAGATCA
    AAAGGTCAAGGAAATATCGAACCAGGAACCACTAAAGATATA
  • Protein Sequence : Show Sequence
    >gi|38371721|ref|NP_941984.1| nucleocapsid protein [Puumala virus]
    MSDLTDIQEDITRHEQQLIVARQKLKDAERAVEVDPDDVNKNTLQARQQTVSALEDKLADYKRRMADAVS
    RKKMDTKPTDPTGIEPDDHLKERSSLRYGNVLDVNAIDIEEPSGQTADWYTIGVYVIGFTLPIILKALYM
    LSTRGRQTVKENKGTRIRFKDDTSFEDINGIRRPKHLYVSMPTAQSTMKAEELTPGRFRTIVCGLFPTQI
    QVRNIMSPVMGVIGFSFFVKDWSERIREFMEKECPFIKPEVKPGTPAQEIEMLKRNKIYFMQRQDVLDKN
    HVADIDKLIDYAASGDPTSPDNIDSPNAPWVFACAPDRCPPTCIYVAGMAELGAFFSILQDMRNTIMASK
    TVGTAEEKLKKKSSFYQSYLRRTQSMGIQLDQRIILLFMLEWGKEMVDHFHLGDDMDPELRGLAQALIDQ
    KVKEISNQEPLKI
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : To investigate the ability of recombinant N (rN, nucleocapsid proteins) from different hantaviruses to elicit cross-protection, we immunized bank voles with rN from Puumala (PUUV), Topografov (TOPV), Andes (ANDV), and Dobrava (DOBV) viruses and subsequently challenged them with PUUV. All animals immunized with PUUV (PUUVsSgp1) and TOPV rN were completely protected (de et al., 2002).
  • Related Vaccine(s): Puumala virus PUUVsSgp1 (NP) protein vaccine
10. S nucleocapsid protein from Dobrava-Belgrade virus
  • Gene Name : S nucleocapsid protein from Dobrava-Belgrade virus
  • Sequence Strain (Species/Organism) : Dobrava-Belgrade virus
  • VO ID : VO_0010960
  • NCBI Gene ID : 2656266
  • NCBI Protein GI : 38505524
  • Locus Tag : DOBVsSp1
  • Genbank Accession : AJ410619
  • Protein Accession : NP_942553
  • Other Database IDs : GI:63030019; Accession:AY961618.1
  • Taxonomy ID : 12506
  • Gene Starting Position : 35
  • Gene Ending Position : 1324
  • Gene Strand (Orientation) : +
  • Protein Name : nucleocapsid protein
  • Protein pI : 7.53
  • Protein Weight : 46162.49
  • Protein Length : 429
  • DNA Sequence : Show Sequence
    >gi|38505523:35-1324 Dobrava virus segment S, complete sequence
    GATGGCAACATTAGAGGAACTCCAAAAAGAAATCAACAACCACGAGGGCCAATTGGTGATAGCCAGGCAG
    AAGGTGAAAGATGCAGAAAAGCAGTATGAAAAGGATCCTGACGACCTGAATAAAAGGGCATTGAGTGACC
    GGGAAAGCATTGCACAATCAATTCAGGGAAAAATAGATGAATTAAGGAGACAGCTGGCTGATCGTGTGGC
    AGCAGGGAAAAACATTGGCAAAGAGAGGGACCCAACTGGACTAGACCCTGGAGATCACCTCAAAGAGAAG
    TCAATGCTCAGTTATGGAAATGTCATTGACCTCAACCATCTTGACATTGATGAACCTACAGGGCAAACCG
    CAGACTGGCTGAGCATTGTGGTCTACCTGACATCATTCGTGGTTCCAATATTGTTGAAGGCTCTTTACAT
    GCTTACCACCAGAGGGAGACAAACTACTAAAGACAATAAGGGAATGAGAATTCGATTTAAGGATGACAGC
    TCTTTTGAAGATGTGAATGGGATTAGAAAGCCAAAGCACCTGTTCTTGTCAATGCCCAATGCACAATCTA
    GCATGAAGGCAGATGAGATTACACCAGGTCGGTTCAGGACTGCAATTTGTGGACTATACCCAGCCCAGGT
    GAAGGCAAGGAACTTAATCAGTCCTGTGATGAGTGTGATTGGGTTTTTAGCCCTTGCAAAGAACTGGACA
    GAGCGGGTTGAGGAATGGCTTGACCTCCCGTGCAAGCTACTATCTGAGCCATCTCCAACGTCTTTGACCA
    AAGGCCCATCCACCAATCGTGACTACTTGAATCAAAGACAAGGAGCGCTTGCAAAAATGGAAACAAAAGA
    AGCTCAGGCTGTGAGGAAACATGCCATAGATGCTGGCTGCAACCTTATCGACCATATAGACTCACCATCA
    TCAATCTGGGTCTTTGCAGGAGCACCCGACAGATGCCCTCCTACCTGCCTGTTCATTGCAGGCATGGCAG
    AGCTAGGTGCATTCTTTGCTGTTCTCCAGGATATGAGGAACACCATCATGGCGTCAAAAACTATCGGAAC
    ATCTGAGGAGAAGCTAAAGAAGAAATCATCTTTTTACCAATCTTACCTACGGAGGACACAATCTATGGGG
    ATACAACTGGACCAGCGCATCATCGTGCTCTTCATGGTTGACTGGGGAAAAGAGGCAGTTGATAGTTTTC
    ATCTTGGTGATGATATGGATCCTGAGCTCCGGGGCCTGGCACAGGCATTAATTGATCAAAAAGTGAAGGA
    AATATCTAATCAGGAACCGCTTAAGCTTTA
  • Protein Sequence : Show Sequence
    >gi|38505524|ref|NP_942553.1| nucleocapsid protein [Dobrava-Belgrade virus]
    MATLEELQKEINNHEGQLVIARQKVKDAEKQYEKDPDDLNKRALSDRESIAQSIQGKIDELRRQLADRVA
    AGKNIGKERDPTGLDPGDHLKEKSMLSYGNVIDLNHLDIDEPTGQTADWLSIVVYLTSFVVPILLKALYM
    LTTRGRQTTKDNKGMRIRFKDDSSFEDVNGIRKPKHLFLSMPNAQSSMKADEITPGRFRTAICGLYPAQV
    KARNLISPVMSVIGFLALAKNWTERVEEWLDLPCKLLSEPSPTSLTKGPSTNRDYLNQRQGALAKMETKE
    AQAVRKHAIDAGCNLIDHIDSPSSIWVFAGAPDRCPPTCLFIAGMAELGAFFAVLQDMRNTIMASKTIGT
    SEEKLKKKSSFYQSYLRRTQSMGIQLDQRIIVLFMVDWGKEAVDSFHLGDDMDPELRGLAQALIDQKVKE
    ISNQEPLKL
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Study compared the immunogenicity and protective efficacy of recombinant DOBV nucleocapsid protein (rDOBV N, S) given with Alum or Freund's as adjuvant, or PBS, in C57/BL6 mice. Mice receiving rDOBV N with Freund's adjuvant were protected from challenge (75% protected) (Klingstrom et al., 2004).
  • Related Vaccine(s): Dobrava-Belgrade virus S nucleocapsid protein vaccine , Recombinant DOBV nucleocapsid protein (rDOBV N)
11. SNVsSgp1
  • Gene Name : SNVsSgp1
  • Sequence Strain (Species/Organism) : Sin Nombre virus
  • VO ID : VO_0011087
  • NCBI Gene ID : 2943142
  • NCBI Protein GI : 38371726
  • Locus Tag : SNVsSgp1
  • Genbank Accession : L37904
  • Protein Accession : NP_941975
  • Taxonomy ID : 37705
  • Segment No : segment S
  • Gene Starting Position : 42
  • Gene Ending Position : 1328
  • Gene Strand (Orientation) : +
  • Protein Name : nucleocapsid protein
  • Protein pI : 6.64
  • Protein Weight : 45894.2
  • Protein Length : 428
  • Protein Note : putative
  • DNA Sequence : Show Sequence
    >gi|38371725:42-1328 Sin Nombre virus chromosome S segment, complete genome
    AATGAGCACCCTCAAAGAAGTGCAAGACAACATCACTCTCCACGAACAACAACTCGTGACTGCCAGGCAG
    AAGCTCAAAGATGCAGAAAGAGCGGTGGAATTGGACCCCGATGATGTTAACAAAAGCACATTACAGAGCA
    GACGGGCAGCTGTGTCTGCATTGGAGACCAAACTCGGAGAACTTAAGCGGGAACTGGCTGATCTTATTGC
    AGCTCAGAAATTGGCTTCAAAACCTGTTGATCCAACAGGGATTGAACCTGATGACCATCTAAAGGAAAAG
    TCATCATTGAGATATGGAAATGTCCTTGATGTAAATTCCATTGACTTAGAAGAGCCAAGTGGGCAAACAG
    CTGATTGGAAATCCATCGGACTCTACATTCTAAGTTTCGCATTACCGATTATTCTTAAAGCCTTGTACAT
    GTTATCTACTAGGGGCCGTCAAACAATCAAAGAAAACAAGGGAACAAGAATTCGATTCAAGGATGATTCA
    TCTTATGAAGAAGTCAATGGGATACGTAAGCCAAGACATCTGTATGTTTCTATGCCAACTGCCCAGTCTA
    CAATGAAAGCAGATGAGATTACTCCCGGGAGGTTCCGTACAATTGCTTGTGGATTATTCCCAGCCCAAGT
    CAAAGCAAGGAATATTATCAGTCCTGTCATGGGTGTGATTGGCTTTAGTTTTTTTGTGAAAGATTGGATG
    GAAAGGATTGATGACTTCCTGGCTGCACGTTGCCCATTTCTGCCTGAGCAGAAAGACCCTAGAGATGCTG
    CATTGGCAACTAATAGAGCCTATTTTATAACACGTCAATTACAGGTTGATGAGTCAAAGGTTAGTGATAT
    TGAGGACCTGATTGCTGATGCAAGGGCTGAGTCTGCCACTATATTCGCAGATATTGCTACTCCTCATTCA
    GTTTGGGTCTTTGCATGTGCTCCAGATCGTTGTCCACCTACAGCATTATATGTGGCCGGGATGCCGGAAC
    TGGGTGCATTTTTTGCTATTCTCCAGGATATGAGGAACACCATAATGGCATCCAAATCTGTGGGGACATC
    TGAAGAGAAATTGAAGAAGAAATCAGCATTCTACCAGTCATACTTAAGACGTACTCAGTCAATGGGAATT
    CAACTGGACCAGAAGATAATCATCTTATACATGAGCCATTGGGGAAGAGAGGCCGTGAATCACTTCCATC
    TTGGAGATGATATGGATCCTGAGCTTAGGGAACTTGCCCAGACCCTTGTAGATATCAAGGTCAGGGAAAT
    CTCTAACCAAGAACCACTTAAACTTTA
  • Protein Sequence : Show Sequence
    >gi|38371726|ref|NP_941975.1| nucleocapsid protein [Sin Nombre virus]
    MSTLKEVQDNITLHEQQLVTARQKLKDAERAVELDPDDVNKSTLQSRRAAVSALETKLGELKRELADLIA
    AQKLASKPVDPTGIEPDDHLKEKSSLRYGNVLDVNSIDLEEPSGQTADWKSIGLYILSFALPIILKALYM
    LSTRGRQTIKENKGTRIRFKDDSSYEEVNGIRKPRHLYVSMPTAQSTMKADEITPGRFRTIACGLFPAQV
    KARNIISPVMGVIGFSFFVKDWMERIDDFLAARCPFLPEQKDPRDAALATNRAYFITRQLQVDESKVSDI
    EDLIADARAESATIFADIATPHSVWVFACAPDRCPPTALYVAGMPELGAFFAILQDMRNTIMASKSVGTS
    EEKLKKKSAFYQSYLRRTQSMGIQLDQKIIILYMSHWGREAVNHFHLGDDMDPELRELAQTLVDIKVREI
    SNQEPLKL
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Study used a deer mouse infection model to test the protective efficacy of genetic vaccine candidates for Sin Nombre (SN) virus that were known to provoke immunological responses in BALB/c mice. Protective epitopes were localized in each of four overlapping cDNA fragments that encoded portions of the SN virus G1 glycoprotein antigen; the nucleocapsid gene (SNVsSgp1) also was protective (Bharadwaj et al., 2002).
  • Related Vaccine(s): Sin Nombre virus DNA vaccine encoding SNVsSgp1 (NP)
1. Ighg1
2. Il2
  • Gene Name : Il2
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 16183
  • NCBI Protein GI : 7110653
  • Locus Tag : DN-144H19.3
  • Genbank Accession : AF195954
  • Protein Accession : NP_032392
  • Taxonomy ID : 10090
  • Chromosome No : 3
  • Gene Starting Position : 37120712
  • Gene Ending Position : 37125953
  • Gene Strand (Orientation) : -
  • Protein Name : interleukin 2
  • Protein pI : 4.63
  • Protein Weight : 18506.61
  • Protein Length : 169
  • Protein Note : Also known as Il-2
  • DNA Sequence : Show Sequence
    >gi|372099107:37120712-37125953 Mus musculus strain C57BL/6J chromosome 3, GRCm38 C57BL/6J
    ATTTTTTTTTAGAGGAGAGCTTTATTTCTTGAAAACACTGATTAACATAGAGTTCACAGGAATAACTGAG
    AAGTTATTTTAGCGCTTACTTTGTGCTGTCCTAAAAATGACAGACATCTGAGCTTATTTATATTTGAATC
    ATCTAAATACTTTTATTAATGAGTCTACCTACACATGATATTTAACAATTCAATATAATAAATAATTTCA
    GATAAATAGTTTAAAACATTTTTGAGCCCTTGGGGCTTACAAAAAGAATCTTTAAAGATCCATATTTATC
    ATCTGAAGACTAGTAGTTACAAAAGATAGTAAACAATACATCCAAAAATAAATTAAAGTTAAATATTTAA
    ATAAATAGAGAGCCTTATGTGTTGTAAGCAGGAGGTACATAGTTATTGAGGGCTTGTTGAGATGATGCTT
    TGACAGAAGGCTATCCATCTCCTCAGAAAGTCCACCACAGTTGCTGACTCATCATCGAATTGGCACTCAA
    ATGTGTTGTCAGAGCCCTAAAAAAGAATATAAAATTGTAGGCTAAGGTAGCTTACTTTGCATATAATTAT
    TCTTCACGGAAGCTTTTAGGCATTTATTTTAACACTGGTTAAATATATTGAACATTCACATTTCTGAAAT
    GATCACAATTATTGGGTTATGTTTTATTATGATATCAAATGGTAAAGCATAAAAAATAAAGCTCTCCAGA
    GTTGATTACCAACGAGCATTTGATGGGAACACTGAACACTTCTGTAGAATTCAGTTGCTTGACCACTTTT
    TCTCTGGTAAGTGTACACAGCTATGCATCAATTTAGGCTTCAGGAATGGAGAAATGATACTTGTTATATG
    TTCTTTGCTAAATCTTAAGAGTCTATTATTCAATTCTTTCCCCCCCAAGTCAGAATGGGAACAACCCAGA
    GTAGGTTAGGACAAGCATCTATTGGGGGAAATTTGGAGAATTTTGTTATAGATATACCTACCCTGATACC
    AGTGTAGATGAATCACAAAGTTTGTACATGTATAAATATTATAAATTTGTTCTGTGGATTAGCTTTTTGA
    AAGCTAACCCTCTTTGCTAAAGGAGATATTTTAATTCTGTTTTTAGGTGACAAGCTGAGAAGGAAATATT
    TTGACAAATTTATGGGATGGCTTTTCCAAATCTGACTAATTCCTTGTAAGTCAAATGAGGCAGATTATTC
    CTTTTAAATAAATACTCCTTTTCAAATAAGCTGCTGTGGTCTTATATACCCTCTTTACATAGCTACTTCA
    ATATTCTAATGTCTTGAATTTTTCATTTTTAAAAATATGTGGCCCTTGAAACATTTTTCTAGTTCTCATG
    TAGCTCTAAAGTTTGTACCATTCATTAGGGGTGAACTTTCTGATGTTGGCCATAGATTTTAGAGCATCCA
    TCTTTGCATACGTAAGTACTCGATTTTAGAGCATCCATCTTAGCATACGTAAGTACTCACACCTTTCAAC
    GTCTAGATGATGTGTATTTCAGCCTGCTTTAAAAACCTCAAATGGAAGCTGGGCAGTGGTGGTGCAGGCC
    TTTAATCCCAGCACTTGGGAGGCAGAGGCAGGCGGATTTCTGAGTTCGAGGCCAGCCTGGTCTACAGAGT
    GAGTTCCAGGACAGCCAGGGCTACACAGAGAAATCCTGTCTCAAAAAAACAAACAAACAAACAAACAAGA
    AACAAACAAACAAAAAAAACAAAAACAAACAAAACAAAACCTCAAATGGAAACAGTGCACTGAAATGTGA
    CTTTGGTTTGGAAAGGACTAGCCCACACCCTCTTGGAGGCTTGCTGCTACTGTCTCACCAGAGTCCATGA
    TTCTTGTGCATTTAAAAACAAAGCTCTGCAGTGGGCTCTCCCCGTCCTGCTCTGTCCATTTTAATGGCTG
    CCATTTTTGGAGAGAAATGTCTGTTTTTCTACCAATACCAGCACAACTTCTCTGGAAAAACTTTTCAGAT
    AATTTTTTCTGATCTGATGAATGTAACACCAGCAAGAGTTGCTTGTTTCTTGTGGAATTCTACTCCGTGC
    TTTCTCTCACATCCAGTTCTATGCTGGTGTGGAGGGAGCAGAGTGTTCATGTTCCCAGTTTCCTTGCAGG
    TGATGGTAGGTGGAAATTCTAGCATCATCCTACAGTGGAAGGATTCACTTGCACAGTGACTTTAAACTTT
    GGCTGACTAAATGCACAGAACCCATCAAAGACCAGAAATGGCAAGCCACTTAAAAATGCATTTCTTCTCT
    ATTTTATTTCCAGATTAGCAAATAAAGCAACACCTTACCTTTAGTTTTACAACAGTTACTCTGATATTGC
    TGATGAAATTCTCAGCATCTTCCAATTGAAAGCTTTTGCTTTGAGTCAAATCCAGAACATGCCGCAGAGG
    TCCAAGTTCATCTTCTAGGCACTGAAGATCTTTCAATTCTGTGGCCTAGAGGAGTAATAAGCTTAACCAT
    CAGCTCAGCTCACCACATACTGAAGAGCCAGAAAGTTAGTCTGCAGTCTCTCTAATCAAGAGAAGGCAGC
    ACATAGCTTTTACCACTCCCTGTCCTCTGTAAAGGGGGACTGAGGTAATCGATGCCATAAATCTAGAAGA
    GCAAGAGCTCACAACCATAAGGGTCACCTTGACTGTTAGGCCACTCTAGTGAGCTCTTCTGGCTTCATTA
    GACTTTGTAAAAAGTCTGTGTTTCTCTACCAATGCATAGCACAAGTTCAGACTATTGTTCCAATCTACAA
    AGAAATCTGCAAGGTTCACATTCTAATATCTAATCGCAGAGTTGAGAATCACAGAAGGGTAAGGGACAGG
    AATCCTTGGATGCCAACTGTCATAGGCCTAAATCTTACAGATTAGGTTATCATGGCCCTGACTGAGGGGT
    GTCAAGATAGCCAGGAAGACACATGTAATATTTTTTAAATTTATACTTCTCTGCAATTACTAAAGATGAG
    TTTTTTAAAAACCCATATGTCAAGCTAGGAAGATGGCTTTTAAGGTAAAGGTACCTGCCACCAAACTTGA
    TGATTTGAGTTCAATTGCAGTGACCCACCCACATTGTGGAAAGAATGGCCCAACTTTCATATTTCGTCTT
    CTGACCTCCACAGTTACACTGTGATACACATGCACCTCCACACATACATACATACATACATACATACATA
    CATACATACATACATACATACATACATAAAATGTAAAATCTATTTGTCCCAATGAAAAAAGTCATAACAT
    TTTGGCAGAACACTTGGGAGAATTTTTCTGATCCATGTATGAAATAATGTTTAAATACATCATGCATACT
    TACATACATATACAGGGAAAAAGGATATTGTCTAGCTCTATAGTACACTATGATTTCCATAAAGTCAGCT
    GCTTTAAGTCTACAGTGAACTGTGTTATCTCCATTTTACCAAGTCTCACAATCAGTGTCTTTCCCACAAC
    CACATGAACGGGGAGCAAGGGTGGCCCGGTCGGTCGGTCGCTCCTTTCATTAACCACAGCCTTTGAATTA
    CATGCTTCTATTGTTTTTAAAATCTTACATACCGAATGCAGGTTAAATGAAAACATCAGCAGAATTTACC
    ACATTACTCTTGTTTTCAATAATTATTTTAAAACTTAGATTTCTAGGAATTTCACCACTCTCTAAATTAA
    CATGATCTCTGTTGTTTCTCTAACAATCCTTAGAGGAAGAGGTTTGACAAGATAACACGTAGTTCCTGAT
    TGGTCTGCTATTGACCTTCCAACTTGTTATGGTGTGTCTTGGGTATTCAGTGTGGAGCTCCTTCCCTCAC
    AGAACTCTCCAGTTTGTTACTGTGGGAGCTGAACATTATGTGACTGTAATTAAGCTGGAAGAGCAACTGG
    GGCCTTTCTTTTTCATCTCCTGTAGAACAGCTAGAGGCAAAGTTCCCCTGACTCAATAGGAATGGGTCAA
    CAGCTGCCTCTTTGTCCCCTTAGATCCCATTTTGCTCTAGGCTTGGATTTACTTGGGACAAGCTCTTTCT
    AGGACCAAAGTTATCCATTCTCTTTTGACTTTCGGGACTAGAGCAAATTTCTACCCTTGCTGGAGTTCTA
    AGAGCTTGTGTAAGCTGTTTTGTATCACACAACATTCTGCCTCCAAAGGAGACCAAAAAACCTTTCAATA
    TTGAGAGATAGTATCATGTAGTAATATTACAGCTCTCTAGTTCCACTAGTTAAAAGAGACTGTATAAATC
    CAAAATTGTTTTATACATCTCGGACTTCTTCTCTAGCACTAATAGTGTGTTTATGTGCTGTTGGCCAGAC
    ACTGTTCTGAAACCTGACAAGTGATAAGCATAGCAATGATCATTTATGTAAGTGGGTGAATGAGCATAGA
    CAACTTCCTGAGGCCATGAGAGCTAGGCCCTAGCAGGGCTGGACTCCACTGCAGATCATTGGCCCTAGAA
    TCTTAACATTGGTTATGCTGCTCCTCAAAAATGCAGTCATAGGAATCATTCTTAAAACAGTAAAGTGTGT
    GTAAAATGAGACCCTCTCAAGTCAATTTTTACATTTAAGAAGCTGAAATAATGCACCTCTCTCAAATATC
    TGTAGGACAAGCATAAAACAGAAATCAACAGTCTTTAAATTATCCCAGCATCAAAATGCAATCATCTTGC
    ATTTTCTTCTCATTCCCTTTCCCAACACATAAATACACAGGAAAAATGTAAAGAAAACCATTTAAAAGAA
    GTACCATTGTCAAGATTTTTTTACAGAGAGATATCAGAGAAACTTATTTTCTTCAGATGAGGTACTATTC
    ATCTGGTCACATGTTATTTACACGTTATACACATGTATGTTACTTTGAATTCATTAGAGCACCAGTTAAA
    CACAGAAACTCACTCACCTGCTTGGGCAAGTAAAATTTGAAGGTGAGCATCCTGGGGAGTTTCAGGTTCC
    TGTAATTCTGAGAAAGCGTAACACATTATTATTAAAGGTTATTAAACACAGCCTTTGGCAAGAAAGCTAA
    AGGTATTGCCTATAGATGGGATGGCTGTGCACTTACCTCCATCCTGCTCAGGAGCTCCTGTAGGTCCATC
    AACAGCTGCTCCAGGTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGTGCTTCCGCTGTAGAGC
    TTGAAGTGGAGCTTGAAGTGGGTGCGCTGTTGACAAGGAGCACAAGTGTCAATGTGACACAGGATGCGAG
    CTGCATGCTGTACATGCCTGCAGGACTTGAGGTCACTGTGAGGAGTGATTAGCAAGGGTGAT
  • Protein Sequence : Show Sequence
    >gi|7110653|ref|NP_032392.1| interleukin-2 precursor [Mus musculus]
    MYSMQLASCVTLTLVLLVNSAPTSSSTSSSTAEAQQQQQQQQQQQQHLEQLLMDLQELLSRMENYRNLKL
    PRMLTFKFYLPKQATELKDLQCLEDELGPLRHVLDLTQSKSFQLEDAENFISNIRVTVVKLKGSDNTFEC
    QFDDESATVVDFLRRWIAFCQSIISTSPQ
  • Molecule Role : Vaximmutor
  • Related Vaccine(s): Dobrava-Belgrade virus S nucleocapsid protein vaccine
3. Il4 (interleukin 4)
  • Gene Name : Il4 (interleukin 4)
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 16189
  • NCBI Protein GI : 10946584
  • Locus Tag : RP23-188H3.4
  • Genbank Accession : NM_021283.1
  • Protein Accession : NM_021283.1
  • Taxonomy ID : 10090
  • Gene Strand (Orientation) : ?
  • Protein Name : IL-4, Interleukin 4
  • DNA Sequence : Show Sequence
    >gi|10946583|ref|NM_021283.1| Mus musculus interleukin 4 (Il4), mRNA
    GGATCCCCGGGCAGAGCTGGGGGGGGATTTGTTAGCATCTCTTGATAAACTTAATTGTCTCTCGTCACTG
    ACGGCACAGAGCTATTGATGGGTCTCAACCCCCAGCTAGTTGTCATCCTGCTCTTCTTTCTCGAATGTAC
    CAGGAGCCATATCCACGGATGCGACAAAAATCACTTGAGAGAGATCATCGGCATTTTGAACGAGGTCACA
    GGAGAAGGGACGCCATGCACGGAGATGGATGTGCCAAACGTCCTCACAGCAACGAAGAACACCACAGAGA
    GTGAGCTCGTCTGTAGGGCTTCCAAGGTGCTTCGCATATTTTATTTAAAACATGGGAAAACTCCATGCTT
    GAAGAAGAACTCTAGTGTTCTCATGGAGCTGCAGAGACTCTTTCGGGCTTTTCGATGCCTGGATTCATCG
    ATAAGCTGCACCATGAATGAGTCCAAGTCCACATCACTGAAAGACTTCCTGGAAAGCCTAAAGAGCATCA
    TGCAAATGGATTACTCGTAGTACTGAGCCACCATGCTTTAACTTATGAATTTTTAATGGTTTTATTTTAA
    TATTTATATATTTATAATTCATAAAATAAAATATTTGTATAATGT
  • Protein Sequence : Show Sequence
    >gi|10946584|ref|NP_067258.1| interleukin 4 [Mus musculus]
    MGLNPQLVVILLFFLECTRSHIHGCDKNHLREIIGILNEVTGEGTPCTEMDVPNVLTATKNTTESELVCR
    ASKVLRIFYLKHGKTPCLKKNSSVLMELQRLFRAFRCLDSSISCTMNESKSTSLKDFLESLKSIMQMDYS
  • Molecule Role : Vaximmutor
  • Molecule Role Annotation : IL-4 plays an important role in Th2 immune response.
  • Related Vaccine(s): Dobrava-Belgrade virus S nucleocapsid protein vaccine
IV. Vaccine Information
1. Andes virus vaccine using adenovirus viral vector expressing ANDV NP
a. Vaccine Ontology ID:
VO_0011561
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Antigen
Andes virus nucleocapsid protein (ANDVsSgp1)
e. Gene Engineering of ANDVsSgp1
  • Type: Recombinant vector construction
  • Description: Nonreplicating (E1− E3−) Ad vectors expressing ANDV proteins were constructed using the AdMax HI-IQ system (Microbix, Toronto, Canada). The ANDV GN, GC, GPC, and N open reading frames were PCR amplified from plasmids containing the appropriate cDNAs derived from a Chilean ANDV isolate, strain 9717869. AdEmpty was constructed using plasmid pDC316(io) containing no ANDV sequences. These pDC316(io)-based ANDV plasmids were cotransfected with plasmid pBHGloxΔE1,3Cre, containing the remainder of the Ad5 genomic plasmid, into 293 IQ cells. Supernatants were collected after 6 to 8 days, and the presence of Ad vectors expressing the ANDV proteins (designated AdN, AdGN, AdGC, and AdGPC) was confirmed by immunoprecipitation. Ad vectors were plaque purified, propagated in large-scale infections in 293 IQ cells, and purified using standard CsCl gradient methods (Safronetz et al., 2009).
  • Detailed Gene Information: Click here.
f. Vector:
Nonreplicating adenovirus (Ad) vectors
g. Immunization Route
Intraperitoneal injection (i.p.)
h. Hamster Response
  • Host Strain: Syrian gold
  • Vaccination Protocol: Syrian golden hamsters (Mesocricetus auratus) (4- to 6-week-old males; Charles River, Pointe Claire, Canada) were group housed in microisolator units situated in the biosafety level 4 area of the National Microbiology Laboratory, Public Health Agency of Canada. Prior to vaccine experiments, the 50% lethal dose (LD50) for i.p. injections of ANDV in hamsters was established by inoculating anesthetized animals with 0.8 to 80,000 FFU (using 10-fold dilutions) of ANDV. Hamsters were monitored twice daily for clinical signs of illness according to an approved scoring sheet (ruffled fur, lethargy, inappetence, and labored breathing). For vaccination, hamsters were anesthetized with isoflurane, a preimmunization blood sample was collected, and the animals were immunized with the Ad vectors using 108 (293 cell) PFU of each vector diluted in 100 μl phosphate-buffered saline at two sites in the hind-leg musculature (Safronetz et al., 2009).
  • Challenge Protocol: After 28 days, a second blood sample was collected and hamsters were challenged with ANDV by i.p. injection of 100 LD50s (equivalent to 154 FFU). Hamsters were examined twice daily for signs of illness. Survivors were monitored for 40 to 45 days and then anesthetized and exsanguinated via cardiac puncture (Safronetz et al., 2009).
  • Efficacy: Nonreplicating adenovirus (Ad) vectors that express Andes hantavirus (ANDV) nucleocapsid protein (AdN, ANDVsSgp1) or glycoproteins (AdG(N) and AdG(C)) were constructed . When administered once, all three Ad vectors, individually or in combination, elicited a robust immune response that protected Syrian hamsters from a lethal ANDV infection that mimics the pulmonary disease seen in humans. No vaccinated animal died, and there were no obvious clinical signs of disease (Safronetz et al., 2009).
2. Chimaeric HBV core particles carrying Puumala virus nucleocapsid protein fragments
a. Vaccine Ontology ID:
VO_0004120
b. Type:
Recombinant vector vaccine
c. Antigen
The Puumala virus nucleocapsid protein (Ulrich et al., 1998).
d. Preparation
Chimaeric hepatitis B virus (HBV) core particles were constructed to carry defined fragments of the Puumala virus nucleocapsid protein. Puumala is a European hantavirus (Ulrich et al., 1998).
3. DNA vaccine encoding ANDV glycoproteins
a. Vaccine Ontology ID:
VO_0004119
b. Type:
DNA vaccine
c. Antigen
Both the G1 and G2 glycoproteins are expressed (Custer et al., 2003).
d. Gene Engineering of Hanta_G2
  • Type: Recombinant protein preparation
  • Description: The Hantavirus G2 glycoprotein was expressed in the DNA vaccine (Custer et al., 2003).
  • Detailed Gene Information: Click here.
e. Vector:
pWRG/HTN-M(x), a customized plasmid built from pWRG7077 (Custer et al., 2003)
f. Preparation
An expression plasmid, pWRG/AND-M, was constructed that contains the full-length M genome segment of Andes virus (ANDV), a South American hantavirus (Custer et al., 2003).
g. Macaque Response
  • Vaccine Immune Response Type: VO_0000286
  • Efficacy: Rhesus macaques vaccinated by gene gun with pWRG/AND-M developed remarkably high levels of neutralizing antibodies that not only neutralized ANDV (a South American hantavirus) but also cross-neutralized other HPS-associated hantaviruses, including Sin Nombre virus (Custer et al., 2003).
4. Dobrava-Belgrade virus S nucleocapsid protein vaccine
a. Vaccine Ontology ID:
VO_0011512
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
Dobrava-Belgrade virus S nucleocapsid protein
e. Gene Engineering of S nucleocapsid protein from Dobrava-Belgrade virus
  • Type: Recombinant protein preparation
  • Description: His-tagged rDOBV N and recombinant mouse dihydrofolate reductase (rDHFR) was prepared. Freund’s complete adjuvant (FCA) or incomplete (FIA) adjuvant (Sigma, St. Louis, MO) or PBS. A total of 50 μg of recombinant protein was mixed with Alum and FCA/FIA, according to the manufacturers’ descriptions, or PBS, in a total volume of 200 μl per dosage (Klingstrom et al., 2004).
  • Detailed Gene Information: Click here.
f. Adjuvant: Freunds emulsified oil adjuvant
g. Immunization Route
Subcutaneous injection
h. Mouse Response
  • Host Strain: C57/BL6
  • Vaccination Protocol: A total of 50 μg of recombinant protein was mixed with Alum and FCA/FIA, according to the manufacturers’ descriptions, or PBS, in a total volume of 200 μl per dosage. All immunizations and boosters were administered subcutaneously. rDOBV N or rDHFR in Alum, FCA or PBS were administered at day 0. At days 21 and 92, mice were boosted with rDOBV N or rDHFR in Alum, FIA or PBS (Klingstrom et al., 2004).
  • Challenge Protocol: At day 118, all mice were challenged with 10 mouse ID50 of DOBV and 21 days later, all mice were sacrificed. Serum, plasma, and EDTA-blood were drawn at the time points indicated below (Klingstrom et al., 2004).
  • Efficacy: Study compared the immunogenicity and protective efficacy of recombinant DOBV nucleocapsid protein (rDOBV N, S) given with Alum or Freund's as adjuvant, or PBS, in C57/BL6 mice. Mice receiving rDOBV N with Freund's adjuvant were protected from challenge (75% protected) (Klingstrom et al., 2004).
  • Host Gene Response of Il2
    • Gene Response: Significantly higher levels of IL-2 producing cells were found in the group given rDOBV N with Alum as compared to the rDHFR vaccinated groups and PBS vaccinated groups. These results were found in mice peripheral blood mononuclear cells (PBMCs) 113 days after vaccination (Klingstrom et al., 2004).
    • Detailed Gene Information: Click here.
  • Host Gene Response of Il4 (interleukin 4)
    • Gene Response: Significantly higher numbers of IL-4 producing cells were found in the groups given rDOBV N with Freund’s adjuvant as compared to rDOBV N with PBS. These reactions were found in peripheral blood mononuclear cells (PBMCs) 113 days after vaccination (Klingstrom et al., 2004).
    • Detailed Gene Information: Click here.
5. Hantavirus DNA vaccine pWRG/HTN-M
a. Vaccine Ontology ID:
VO_0004576
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Hamsters
e. Gene Engineering of G1 and G2
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
f. Vector:
pWRG7077 (Hooper et al., 2001)
g. Immunization Route
Gene gun
h. Hamster Response
  • Vaccine Immune Response Type: VO_0003057
  • Efficacy: All of the hamsters that were vaccinated with pWRG/HTN-M were protected against infection as defined by an absence of a postchallenge N-specific antibody response. In addition, the pre- and postchallenge PRNT titers differed by ≤4-fold. In contrast, all of the negative control hamsters, whether they were vaccinated with pWRG7077 or remained unvaccinated, were infected, as evidenced by the development of N-specific antibodies and neutralizing antibodies postchallenge (Hooper et al., 2001).
6. Puumala virus PUUVsSgp1 (NP) protein vaccine
a. Vaccine Ontology ID:
VO_0011400
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
Puumala virus nucleocapsid protein (PUUVsSgp1)
e. Gene Engineering of PUUVsSgp1
  • Type: Recombinant protein preparation
  • Description: N proteins from PUUV, TOPV, ANDV, and DOBV, carrying a polyhistidine tag to facilitate protein purification, were produced in Escherichia coli cells. The N ORF of PUUV, TOPV, and DOBV were cloned into the pQE-32 vector (Qiagen, Hilden, Germany), while the N ORF of ANDV was cloned into pRSET (R&D Systems Europe, Oxford, United Kingdom). An irrelevant protein, mouse dihydrofolate reductase (DHFR) (Qiagen), provided by the manufacturer and expressed in the same system, was used as a negative control protein (de et al., 2002).
  • Detailed Gene Information: Click here.
f. Adjuvant: complete Freunds adjuvant
g. Adjuvant: incomplete Freunds adjuvant
h. Bank vole Response
  • Vaccination Protocol: To asses the immunogenicity and protective capacity of the expressed rN proteins, 4- to 10-week-old bank voles, derived from a PUUV-free colony established with animals captured in Sweden, were immunized with purified PUUV, TOPV, ANDV, or DOBV rN or DHFR control protein. Bank voles were immunized three times with 50 μg of protein at intervals of 3 weeks. The animals were injected with protein emulsified in Freund's complete adjuvant, incomplete Freund's adjuvant, and phosphate-buffered saline (PBS), respectively (de et al., 2002).
  • Challenge Protocol: Bank voles were challenged subcutaneously 2 weeks after the last immunization with approximately 20 50% infective doses of wild-type PUUV (strain Kazan) (de et al., 2002).
  • Efficacy: To investigate the ability of recombinant N (rN, nucleocapsid proteins) from different hantaviruses to elicit cross-protection, we immunized bank voles with rN from Puumala (PUUV), Topografov (TOPV), Andes (ANDV), and Dobrava (DOBV) viruses and subsequently challenged them with PUUV. All animals immunized with PUUV (PUUVsSgp1) and TOPV rN were completely protected (de et al., 2002).
7. Recombinant DOBV nucleocapsid protein (rDOBV N)
a. Vaccine Ontology ID:
VO_0004102
b. Type:
Subunit vaccine
c. Gene Engineering of S nucleocapsid protein from Dobrava-Belgrade virus
  • Type: Recombinant protein preparation
  • Description: Dobrava hantavirus nucleocapsid protein was used for the vaccine development (Klingstrom et al., 2004).
  • Detailed Gene Information: Click here.
d. Adjuvant: Freunds emulsified oil adjuvant
  • VO ID: VO_0000133
  • Description: Dobrava hantavirus nucleocapsid protein in Freund's adjuvant (Klingstrom et al., 2004).
e. Preparation
Recombinant DOBV nucleocapsid protein (rDOBV N) given with Alum or Freund's as adjuvant (Klingstrom et al., 2004).
f. Virulence
Not virulent
g. Description
Dobrava hantavirus (DOBV) causes a severe form of hemorrhagic fever with renal syndrome (HFRS). Currently there is no therapy or vaccine available for HFRS (Klingstrom et al., 2004).
h. Mouse Response
  • Host Strain: C57/BL6 mice
  • Vaccination Protocol: His-tagged rDOBV N and recombinant mouse dihydrofolate reductase (rDHFR) was emulsified with Imject® Alum (Pierce, Rockford, IL), Freund’s complete adjuvant (FCA) or incomplete (FIA) adjuvant (Sigma, St. Louis, MO) or PBS. A total of 50 μg of recombinant protein was mixed with Alum and FCA/FIA, or PBS, in a total volume of 200 μl per dosage. All immunizations and boosters were administered subcutaneously. rDOBV N or rDHFR in Alum, FCA or PBS were administered at day 0. At days 21 and 92, mice were boosted with rDOBV N or rDHFR in Alum, FIA or PBS. At day 118, all mice were challenged with 10 mouse ID50 of DOBV and 21 days later, all mice were sacrificed. Serum, plasma, and EDTA-blood were drawn at the time points indicated below (Klingstrom et al., 2004).
  • Side Effects: No side effects.
  • Challenge Protocol: All vaccinated mice were subcutaneously challenged with 10 mouse ID50 DOBV at day 118. The challenge did not kill mice. Three weeks after challenge, the mice were sacrificed and serum tested for the presence of neutralizing antibodies (Klingstrom et al., 2004).
  • Efficacy: The immunogenicity and protective efficacy of recombinant DOBV nucleocapsid protein (rDOBV N) given with Alum or Freund’s as adjuvant, or PBS, in C57/BL6 mice, were compared. All mice given Alum or Freund’s seroconverted as did 6/8 mice given rDOBV N with PBS. Reciprocal geometric mean total IgG-titers were 5380, 18,100, and 800, respectively, while the mean IgG1/IgG2a ratios were 17.5, 9.25, and 12, respectively. Furthermore, ELIspot assays showed higher levels of IL-4 producing peripheral blood mononuclear cells (PBMCs) in the group given Alum as compared to the other groups. Interestingly, only mice receiving rDOBV N with Freund’s adjuvant were protected from challenge (75% protected), indicating that the strong Th2-type of immune response induced by Alum against rDOBV N did not induce protection in mice (Klingstrom et al., 2004).
8. rVSVΔG-ANDV-GPC
a. Vaccine Ontology ID:
VO_0004662
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Immunization Route
Intramuscular injection (i.m.)
f. Hamster Response
  • Vaccination Protocol: Syrian hamsters were immunized with a single injection of VSVΔG/ANDVGPC (Brown et al., 2011).
  • Vaccine Immune Response Type: VO_0000287
  • Challenge Protocol: After immunization, the hamsters were challenged at 28, 14, 7, or 3 days postimmunization with a lethal dose of ANDV (Brown et al., 2011).
  • Efficacy: The hamsters were fully protected against the disease; however, the mechanism of protection seems to differ depending on when the immunization occurs. Administration of the vaccine at 7 or 3 days before challenge also resulted in full protection but with no specific neutralizing humoral immune response, suggesting a possible role of innate responses in protection against challenge virus replication. Administration of the vaccine 24 h postchallenge was successful in protecting 90% of hamsters and again suggested the induction of a potent antiviral state by the recombinant vector as a potential mechanism (Brown et al., 2011).
9. Seoul virus vaccine rCAV-2-Gc
a. Vaccine Ontology ID:
VO_0011402
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Antigen
Seoul virus Gc glycoprotein
e. Gene Engineering of Gc
  • Type: Recombinant protein preparation
  • Description: The Gc protein expressed by rCAV-2-Gc in MDCK cells was evaluated by a SEOV-specific indirect IFA. MDCK cells grown on 15 mm glass coverslips in 12-well culture plates were infected with rCAV-2-Gc or CAV-2 at an m.o.i. of 20. After 48 h infection, the coverslips were rinsed once with PBS (pH 7.4), fixed with acetone for 10 min at room temperature and then reacted with rabbit anti-SEOV polyclonal antiserum and washed three times with PBS. The fixed monolayers were incubated at 37 °C for 30 min in a moist chamber with donkey anti-rabbit IgG labelled with fluorescence isothiocyanate (Amersham). The coverslips were rinsed three times with PBS. Cell monolayers that bound the antibody were covered with glycerine and examined for specific fluorescence under a Zeiss Axioplan fluorescence microscope. Expression of SEOV Gc in MDCK cells infected with rCAV-2-Gc was identified by Western blotting. rCAV-2-Gc-infected cell lysates were separated by 12 % SDS-PAGE, and the proteins transferred to nitrocellulose membrane (Pall Corporation) and probed with positive serum against SEOV and HRP-labelled goat anti-mouse IgG antibody (Sigma) (Yuan et al., 2010).
  • Detailed Gene Information: Click here.
f. Vector:
replication-competent recombinant canine adenovirus type 2
g. Immunization Route
Intramuscular injection (i.m.)
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were randomly assigned to four experimental groups (20 mice per group). Group I was intramuscularly inoculated once with 0.1 ml rCAV-2-Gc (108.0 p.f.u. ml–1); group II received 0.1 ml CAV-2 (108.2 p.f.u. ml–1) intramuscularly as a negative control; group III were inoculated intramuscularly with one dose of HFRS bivalent purified vaccine Youerjian (0.5 ml per dose; GuangDong HongMing Biological Science and Technology Co.) as a positive-control; and group IV were injected with 0.1 ml PBS as a negative control (Yuan et al., 2010).
  • Challenge Protocol: At the end of the trial, all mice were injected intramuscularly with SEOV strain CC-2 diluted in 0.2 ml PBS. The challenge dose for each virus was 2000 p.f.u. This dose is 1000 50 % infective doses for SEOV. At 14 days after challenge, the mice were sacrificed by CO2 asphyxiation, as approved by the China Small Animal Protection Association. Pre- and post-challenge sera were evaluated for the presence of N-specific antibodies by ELISA and for the presence of neutralizing antibodies by FRNT. Detecting post-challenge N-specific antibody indicated that the mice were infected with the challenge virus (Yuan et al., 2010).
  • Efficacy: eplication-competent recombinant canine adenovirus type 2 expressing the Gc protein of SEOV (rCAV-2-Gc) in BALB/c mice induced complete protection against a intensive infectious challenge with ~1,000 50% infective doses (ID50) for SEOV strain CC-2 (Yuan et al., 2010).
10. Sin Nombre virus DNA vaccine encoding G1
a. Vaccine Ontology ID:
VO_0011401
b. Type:
DNA vaccine
c. Status:
Research
d. Antigen
Sin Nombre virus envelope glycoprotein G1
e. Gene Engineering of G1
  • Type: DNA vaccine construction
  • Description: Cloned the G1 and G2 glycoprotein genes of SN virus strain CC107 into the CMV expression vector pCMVi (-H3) UBs (Bharadwaj et al., 1999 ). The M segment fragments 3' of the first fragment were prepared in a similar manner, such that each expression construct shared 100 nt of sequence at the 5' end with the 3' end of the fragment that preceded it. The coordinates of each of the ten glycoprotein fragments, designated M-CMV-A thorough -I. We also cloned the entire SN virus N gene in a single fragment in a separate expression construct. The same viral cDNA fragments were cloned into bacterial expression vectors to allow bacterial synthesis of the cognate antigens as fusion proteins, as described (Bharadwaj et al., 1997 ; Yamada et al., 1995 ) (Bharadwaj et al., 2002).
  • Detailed Gene Information: Click here.
f. Vector:
CMV expression vector pCMVi (-H3) UBs
g. Mouse Response
  • Vaccination Protocol: We purified plasmid DNA with an endotoxin-free kit (EndoFree, Qiagen), and dissolved DNA to a concentration of 1 mg/ml in 0·9% NaCl. Five to twelve mice were immunized with each construct three times at 4 week intervals, using 50 µg of plasmid into each set of quadriceps muscles for a total of 100 µg. No adjuvants were used (Bharadwaj et al., 2002).
  • Challenge Protocol: Challenged the mice in the challenge replicate with 5 ID50 of SN77734 by the i.m. route 2 weeks after the third vaccination, a dose that corresponds roughly to 50–200 focus-forming units (Bharadwaj et al., 2002).
  • Efficacy: Study used a deer mouse infection model to test the protective efficacy of genetic vaccine candidates for Sin Nombre (SN) virus that were known to provoke immunological responses in BALB/c mice. Protective epitopes were localized in each of four overlapping cDNA fragments that encoded portions of the SN virus G1 glycoprotein antigen; the nucleocapsid gene also was protective (Bharadwaj et al., 2002).
11. Sin Nombre virus DNA vaccine encoding SNVsSgp1 (NP)
a. Vaccine Ontology ID:
VO_0011543
b. Type:
DNA vaccine
c. Status:
Research
d. Antigen
Sin nombre virus nucleocapsid protein (SNVsSgp1)
e. Gene Engineering of SNVsSgp1
  • Type: DNA vaccine construction
  • Description: Cloned the G1 and G2 glycoprotein genes of SN virus strain CC107 into the CMV expression vector pCMVi (-H3) UBs (Bharadwaj et al., 1999 ). The M segment fragments 3' of the first fragment were prepared in a similar manner, such that each expression construct shared 100 nt of sequence at the 5' end with the 3' end of the fragment that preceded it. The coordinates of each of the ten glycoprotein fragments, designated M-CMV-A thorough -I. We also cloned the entire SN virus N gene in a single fragment in a separate expression construct. The same viral cDNA fragments were cloned into bacterial expression vectors to allow bacterial synthesis of the cognate antigens as fusion proteins (Bharadwaj et al., 2002).
  • Detailed Gene Information: Click here.
f. Vector:
CMV expression vector pCMVi (-H3) UBs
g. Mouse Response
  • Vaccination Protocol: Five to twelve mice were immunized with each plasmid DNA construct three times at 4 week intervals, using 50 µg of plasmid into each set of quadriceps muscles for a total of 100 µg. No adjuvants were used (Bharadwaj et al., 2002).
  • Challenge Protocol: Challenged the mice in the challenge replicate with 5 ID50 of SN77734 by the i.m. route 2 weeks after the third vaccination, a dose that corresponds roughly to 50–200 focus-forming units (Bharadwaj et al., 2002).
  • Efficacy: Study used a deer mouse infection model to test the protective efficacy of genetic vaccine candidates for Sin Nombre (SN) virus that were known to provoke immunological responses in BALB/c mice. Protective epitopes were localized in each of four overlapping cDNA fragments that encoded portions of the SN virus G1 glycoprotein antigen; the nucleocapsid gene (SNVsSgp1) also was protective (Bharadwaj et al., 2002).
12. Topografov virus N protein vaccine
a. Vaccine Ontology ID:
VO_0011403
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
Topografov virus Nucleocapsid protein
e. Gene Engineering of N protein [Topografov virus]
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Adjuvant: complete Freunds adjuvant
g. Adjuvant: incomplete Freunds adjuvant
h. Bank vole Response
  • Vaccination Protocol: To asses the immunogenicity and protective capacity of the expressed rN proteins, 4- to 10-week-old bank voles, derived from a PUUV-free colony established with animals captured in Sweden, were immunized with purified PUUV, TOPV, ANDV, or DOBV rN or DHFR control protein. Bank voles were immunized three times with 50 μg of protein at intervals of 3 weeks. The animals were injected with protein emulsified in Freund's complete adjuvant, incomplete Freund's adjuvant, and phosphate-buffered saline (PBS), respectively (de et al., 2002).
  • Challenge Protocol: Bank voles were challenged subcutaneously 2 weeks after the last immunization with approximately 20 50% infective doses of wild-type PUUV (strain Kazan) (de et al., 2002).
  • Efficacy: To investigate the ability of recombinant N (rN, nucleocapsid proteins) from different hantaviruses to elicit cross-protection, we immunized bank voles with rN from Puumala (PUUV), Topografov (TOPV), Andes (ANDV), and Dobrava (DOBV) viruses and subsequently challenged them with PUUV. All animals immunized with PUUV and TOPV rN were completely protected (de et al., 2002).
13. Truncated Recombinant DoBV Nucleocapsid Proteins (Dob-N rNp)
a. Vaccine Ontology ID:
VO_0004103
b. Type:
Subunit vaccine
c. Adjuvant: Alhydrogel
  • VO ID: VO_0001241
  • Description: Dob-N rNp was emulsified in 2% Alhydrogel (Accurate Chemical & Scientific Corp., Westbury, N.Y., USA). The rNp P40-Dob-N, P40-Dob118 and P40p-Dob118 were administered in sterile PBS (Maes et al., 2006).
d. Preparation
DOBV RNA (strain DOB-90/5) was extracted from infected Vero E6 cells (CRL 1586; ATCC, USA). The genomic RNA of DOBV was reverse-transcribed and PCR amplified in order to generate the entire S-segment, using following oligonucleotide primers: 5'-GCGAATTCGCAACACTAGAGGAACTCCAAAAGG-3' and 5'-CGAAGCTTAGTGGTGGTGGTGGTGGTGAAGTTTGAGCGGCTCC-3'. The amino-terminal part encoding the first 118 amino acids was generated using 5'-CTGGCGCCTAACCGACGTGGTGGTGGTGGTGGTGATTCGAAGC-3' as reverse primer. In all constructs, a histidine (His) tag was introduced at the C-terminal end. PCR fragments were cloned in plasmids pTEX(rP40) or pTEXmp18 respectively with or without the inclusion of the P40 sequence in the construct. Following transformation of the E. coli ICONE 200 strain, the recombinant proteins were produced as intracellular inclusion bodies, recovered, and renatured. The recombinant proteins were purifi ed by metal chelate affinity chromatography using a HisTrap kit (Pharmacia, Puurs, Belgium). Using this protocol, four DOBV rNp constructs were expressed and purified. The complete nucleocapsid protein of DOBV was expressed with or without the addition of the rP40 protein (constructs P40-Dob-N and Dob-N). The amino-terminal part of the DOBV nucleocapsid protein was expressed with the addition of the rP40 protein (construct P40-Dob118) or with the addition of only the periplasmic part of the rP40 protein (construct P40p-Dob118) (Maes et al., 2006).
e. Virulence
Not virulent
f. Mouse Response
  • Host Strain: NMRI mice (Elevage Janvier, Le Genest Saint Isle, France)
  • Vaccination Protocol: Groups of ten 6-week-old NMRI mice (Elevage Janvier, Le Genest Saint Isle, France) were immunized three times subcutaneously with three different concentrations (0.2, 2 and 10 ug) of rNp with intervals of 2 weeks. The animals were injected with Dob-N rNp emulsifi ed in 2% Alhydrogel (Accurate Chemical & Scientific Corp., Westbury, N.Y., USA). The rNp P40-Dob-N, P40-Dob118 and P40p-Dob118 were administered in sterile PBS. Blood was drawn 14 days after each immunization (Maes et al., 2006).
  • Persistence: N/A
  • Side Effects: None.
  • Challenge Protocol: Groups of 10 NMRI mice were immunized three times subcutaneously with 10 ug of the different constructs with intervals of 2 weeks, and were challenged intraperitoneal with DOBV 2 weeks after the last immunization. Three weeks later, all mice were sacrificed and serum samples were collected. Mice immunized three times subcutaneously with 10 ug of rP40 were used as a control group (Maes et al., 2006).
  • Efficacy: All recombinant proteins were found to be highly immunogenic after three immunizations of rNp. The immunizations resulted in the induction of a strong Np-specific IgG response with a predominance of IgG1 over IgG2b and IgG2a, suggesting a mixed Th1/Th2 cell involvement. A specific IgG3 response could not be detected. Mice immunized with recombinant DOBV rNp without rP40 showed lower nucleocapsid-specific antibody responses in comparison with the rP40-conjugated constructs, but all mice were found to be protected against DOBV challenge. The results indicate that the rNp constructs coupled to rP40, represent promising vaccine candidates (Maes et al., 2006).
V. References
1. Bharadwaj et al., 2002: Bharadwaj M, Mirowsky K, Ye C, Botten J, Masten B, Yee J, Lyons CR, Hjelle B. Genetic vaccines protect against Sin Nombre hantavirus challenge in the deer mouse (Peromyscus maniculatus). The Journal of general virology. 2002; 83(Pt 7); 1745-1751. [PubMed: 12075094].
2. Brown et al., 2011: Brown KS, Safronetz D, Marzi A, Ebihara H, Feldmann H. Vesicular stomatitis virus-based vaccine protects hamsters against lethal challenge with Andes virus. Journal of virology. 2011; 85(23); 12781-12791. [PubMed: 21917979].
3. CDC Hantaviruses: CDC Hantaviruses [http://0-www.cdc.gov.mill1.sjlibrary.org/ncidod/diseases/hanta/hps/]
4. Chu et al., 1995: Chu YK, Jennings GB, Schmaljohn CS. A vaccinia virus-vectored Hantaan virus vaccine protects hamsters from challenge with Hantaan and Seoul viruses but not Puumala virus. Journal of virology. 1995; 69(10); 6417-6423. [PubMed: 7666542].
5. Custer et al., 2003: Custer DM, Thompson E, Schmaljohn CS, Ksiazek TG, Hooper JW. Active and passive vaccination against hantavirus pulmonary syndrome with Andes virus M genome segment-based DNA vaccine. Journal of virology. 2003 Sep; 77(18); 9894-905. [PubMed: 12941899 ].
6. de Carvalho Nicacio et al., 2002: de Carvalho Nicacio C, Gonzalez Della Valle M, Padula P, Bjorling E, Plyusnin A, Lundkvist A. Cross-protection against challenge with Puumala virus after immunization with nucleocapsid proteins from different hantaviruses. Journal of virology. 2002 Jul; 76(13); 6669-77. [PubMed: 12050380].
7. Hooper et al., 2001: Hooper JW, Custer DM, Thompson E, Schmaljohn CS. DNA vaccination with the Hantaan virus M gene protects Hamsters against three of four HFRS hantaviruses and elicits a high-titer neutralizing antibody response in Rhesus monkeys. Journal of virology. 2001; 75(18); 8469-8477. [PubMed: 11507192].
8. Klingstrom et al., 2004: Klingstrom J, Maljkovic I, Zuber B, Rollman E, Kjerrstrom A, Lundkvist A. Vaccination of C57/BL6 mice with Dobrava hantavirus nucleocapsid protein in Freund's adjuvant induced partial protection against challenge. Vaccine. 2004 Sep 28; 22(29-30); 4029-34. [PubMed: 15364453].
9. Kruger et al., 2001: Kruger DH, Ulrich R, Lundkvist A A. Hantavirus infections and their prevention. Microbes and infection / Institut Pasteur. 2001 Nov; 3(13); 1129-44. [PubMed: 11709294 ].
10. Lednicky, 2003: Lednicky JA. Hantaviruses. a short review. Archives of pathology & laboratory medicine. 2003 Jan; 127(1); 30-5. [PubMed: 12521363].
11. Maes et al., 2006: Maes P, Keyaerts E, Bonnet V, Clement J, Avsic-Zupanc T, Robert A, Van Ranst M. Truncated recombinant Dobrava hantavirus nucleocapsid proteins induce strong, long-lasting immune responses in mice. Intervirology. 2006; 49(5); 253-60. [PubMed: 16714853].
12. Safronetz et al., 2009: Safronetz D, Hegde NR, Ebihara H, Denton M, Kobinger GP, St Jeor S, Feldmann H, Johnson DC. Adenovirus vectors expressing hantavirus proteins protect hamsters against lethal challenge with andes virus. Journal of virology. 2009; 83(14); 7285-7295. [PubMed: 19403663].
13. Ulrich et al., 1998: Ulrich R, Lundkvist A, Meisel H, Koletzki D, Sjolander KB, Gelderblom HR, Borisova G, Schnitzler P, Darai G, Kruger DH. Chimaeric HBV core particles carrying a defined segment of Puumala hantavirus nucleocapsid protein evoke protective immunity in an animal model. Vaccine. 1998 Jan-Feb; 16(2-3); 272-80. [PubMed: 9607042 ].
14. Yoshimatsu et al., 1993: Yoshimatsu K, Yoo YC, Yoshida R, Ishihara C, Azuma I, Arikawa J. Protective immunity of Hantaan virus nucleocapsid and envelope protein studied using baculovirus-expressed proteins. Archives of virology. 1993; 130(3-4); 365-376. [PubMed: 8517793].
15. Yuan et al., 2010: Yuan ZG, Luo SJ, Xu HJ, Wang XH, Li J, Yuan LG, He LT, Zhang XX. Generation of E3-deleted canine adenovirus type 2 expressing the Gc glycoprotein of Seoul virus by gene insertion of deletion of related terminal region sequences. The Journal of general virology. 2010; ; . [PubMed: 20181748].