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Helicobacter pylori

Table of Contents
  1. General Information
    1. NCBI Taxonomy ID
    2. Disease
    3. Introduction
    4. Microbial Pathogenesis
    5. Host Ranges and Animal Models
  2. Vaccine Related Pathogen Genes
    1. Alkyl hydroperoxide reductase(AhpC) (Protective antigen)
    2. cagA (Protective antigen)
    3. cagL (Protective antigen)
    4. flaA chimeric flagellin (Protective antigen)
    5. ggt (Protective antigen)
    6. gltA (Protective antigen)
    7. hpaA (Protective antigen)
    8. hsp60 (Protective antigen)
    9. hspA (Protective antigen)
    10. hspB (Protective antigen)
    11. katA (Protective antigen)
    12. lpp20 (Protective antigen)
    13. NAP (Protective antigen)
    14. oipA (Protective antigen)
    15. outer membrane protein 26 (Protective antigen)
    16. tpx (Protective antigen)
    17. ureB (Protective antigen)
    18. vacA (Protective antigen)
  3. Vaccine Information
    1. Epivac vaccine
    2. H. pylori AhpC vaccine
    3. H. pylori catalase protein vaccine
    4. H. pylori CFAdE vaccine
    5. H. pylori DNA vaccine pcDNA3.1-hspA
    6. H. pylori DNA vaccine pcDNA3.1-hspB
    7. H. pylori DNA vaccine poipA
    8. H. pylori GltA Protein Vaccine
    9. H. pylori HspA Protein Vaccine
    10. H. pylori HspB Protein Vaccine
    11. H. pylori NAP protein vaccine
    12. H. pylori VacA protein vaccine
    13. H. pylori vaccine encoding UreB
    14. M. S- H. pylori -opm26
    15. SL3261- UreA and UreB
  4. References
I. General Information
1. NCBI Taxonomy ID:
210
2. Disease:
Ulcers
3. Introduction
Helicobacter pylori is a Gram-negative, microaerophilic bacterium that can inhabit various areas of the stomach, particularly the antrum. It causes a chronic low-level inflammation of the stomach lining and is strongly linked to the development of duodenal and gastric ulcers and stomach cancer. Over 80% of individuals infected with the bacterium are asymptomatic.
The bacterium was initially named Campylobacter pyloridis, then renamed C. pylori (pylori = genitive of pylorus) to correct a Latin grammar error. When 16S rRNA gene sequencing and other research showed in 1989 that the bacterium did not belong in the genus Campylobacter, it was placed in its own genus, Helicobacter. The genus derived from the ancient Greek hělix/έλιξ "spiral" or "coil". The specific epithet pylōri means "of the pylorus" or pyloric valve (the circular opening leading from the stomach into the duodenum), from the Ancient Greek word πυλωρός, which means gatekeeper.
More than 50% of the world's population harbor H. pylori in their upper gastrointestinal tract. Infection is more prevalent in developing countries, and incidence is decreasing in Western countries. H. pylori's helix shape (from which the generic name is derived) is thought to have evolved to penetrate the mucoid lining of the stomach (Wiki: Helicobacter pylori).
4. Microbial Pathogenesis
H. pylori are extremely motile bacteria that colonize the mucin layer of the stomach. The bacteria produces urease which helps it to survive the acidic environment of the stomach and also causes inflammation. The bacteria also possess an adhesin that binds the sugars in the mucin layer. H. pylori also has cytotoxins which can induce inflammation (Salyers and Whitt., 2002).
5. Host Ranges and Animal Models
Mice, gnotobiotic piglets, gerbils, and beagle dogs are used as animal model for H. pylori. H. pylori colonizes the human stomach (Salyers and Whitt., 2002).
1. Alkyl hydroperoxide reductase(AhpC)
  • Gene Name : Alkyl hydroperoxide reductase(AhpC)
  • Sequence Strain (Species/Organism) : Helicobacter pylori
  • NCBI Protein GI : EIE30837
  • Taxonomy ID : 210
  • Gene Strand (Orientation) : ?
  • Protein Name : Alkyl hydroperoxide reductase
  • Protein pI : 5.9
  • Protein Weight : 21128.58
  • Protein Length : 266
  • Protein Note : 26695-related strain
  • Protein Sequence : Show Sequence
    >EIE30837.1 Alkyl hydroperoxide reductase [Helicobacter pylori]
    MLVTKLAPDFKAPAVLGNNEVDEHFELSKNLGKNGAILFFWPKDFTFVCPTEIIAFDKRVKDFQEKGFNV
    IGVSIDSEQVHFAWKNTPVEKGGIGQVTFPMVADITKSISRDYDVLFEEAIALRGAFLIDKNMKVRHAVI
    NDLPLGRNADEMLRMVDALLHFEEHGEVCPAGWRKGDKGMKATHQGVAEYLKENSIKL
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Systemic prophylactic immunization with AhpC/alum and mAhpC/alum conferred protection against infection in 55% and 77.3% of mice, respectively (O'Riordan et al., 2012).
2. cagA
  • Gene Name : cagA
  • Sequence Strain (Species/Organism) : Helicobacter pylori
  • NCBI Protein GI : WP_130778457
  • Other Database IDs : CDD:302624
  • Taxonomy ID : 210
  • Gene Strand (Orientation) : ?
  • Protein Name : type IV secretion system oncogenic effector CagA
  • Protein pI : 9.36
  • Protein Weight : 124904.51
  • Protein Length : 1277
  • Protein Note : S-adenosylmethionine-dependent methyltransferases (SAM or AdoMet-MTase), class I; AdoMet-MTases are enzymes that use S-adenosyl-L-methionine (SAM or AdoMet) as a substrate for methyltransfer, creating the product S-adenosyl-L-homocysteine (AdoHcy); cl17173
  • Protein Sequence : Show Sequence
    >WP_130778457.1 type IV secretion system oncogenic effector CagA [Helicobacter pylori]
    MVNETIDQTTTPDQTDFVPQRFINNLQVAFIKVDNAVASFDPDQKPIVDKNDRDNRQAFEKISQLREEYA
    NKAIKNPTKKNQYFSDFINKSNDLINKDNLIAVDSSVESFRKFGDQRYQIFTSWVSLQKDPSKINTQQIR
    NFMENIIQPPISDDKEKAEFLRSAKQSFAGIIIGNQIRSDEKFMGVFDESLKVRQEAEKNEEPAGGDWLD
    IFLSFVFNKKQSSDLKETLNQEPRPDVEQNLATTTTDIQGLPPEARDLLDERGNFFKFTLGDVEMLDVEG
    VADKDPNYKFNQLLIHNNALSSVLMGSHSSIEPEKVSLLYGDNGGPEARHDWNATVGYKNQQGSNVATLI
    NAHLNNGSGLVIAGNENGIKNPSFYLYKEDQLTGLKQAMSQEEIQNKVDFMEFLAKNNAKLDNLSEKEKE
    KFQTEIGNFQKDRKAYLDALGNDHIAFVFKKDPKHLALVTEFGNGEVSYTLKDYGKKQDKALDGETKTTL
    QGNLKYDGVMFVNYSNFKYTNASKSPNKGLGATNGVSHLEANFSKVAVFNLPNLNNLAITNYIRRDLEDK
    LWAKGLSPQEANKLIKDFLNSNKEMVGKVLNFNKAVAGAKNTGNYDEVKKAQKDLEKSLRKREHLEKEVA
    KKLESRNDNKNRMEAKAQANSQKDKIFALINQEASKEARAVAFDPNLKGIRSELLDKLENINKNLKDFGK
    SFDELKNGKNNDFSKAEETLKALKDSVKDLGINPEWISKIENLNAALNDFKNGKNKDFSKVTQAKSDLEN
    SIKDVIINQKITDKVDNLNQAVSETKLTGNFSKVEQALAELKSLSLDLGKNSDLQKSVKNGVNGTLVGNG
    LSKAEATTLTKNFSDIRKELNEKLFGNSNNNNNGLKNNTEPIYAQVNKKKAGQATSPEESVYAQVAKKVS
    VKIDQLNEATSAINRKIDRINKIASAGKGVGGFSGAGRSASPEPIYATIDFDEANQVGFPLRRSAGVNDL
    SKVGLSREQELTRRIGDLNQAVSEAKTGHFGNLEQKIDELKDSTKKNALKLWVESAKQVPTGLQAKLDNY
    ATNSHTRINSNVQSGAINEKATGMLTQKNPEWLKLVNDKVVAHNVGSAPLSDYDKIGFNQKNMKDYSDSF
    KFSTKLNNAVKDIKSSFVQFLTNTFSTGSYSLMKANVEHGVKNTTKSGFQKS
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Compared to non-immunized mice, immunization with Epivac alone or with a Th1 adjuvant significantly reduced H. pylori colonization, and better protection was observed when an adjuvant was used (Li et al., 2012).
  • Related Vaccine(s): Epivac vaccine
3. cagL
  • Gene Name : cagL
  • Sequence Strain (Species/Organism) : Helicobacter pylori
  • NCBI Protein GI : APP94146
  • Taxonomy ID : 210
  • Gene Strand (Orientation) : ?
  • Protein Name : cag pathogenicity island protein CagL
  • Protein pI : 7.34
  • Protein Weight : 26703.9
  • Protein Length : 314
  • Protein Sequence : Show Sequence
    >APP94146.1 cag pathogenicity island protein CagL [Helicobacter pylori]
    MKTLVKNTISSFLLLSVLMAEDITSGLKQLDSTYQETNQQVLKNLDEIFSTTSPSANDKMGEEDALNIKK
    AAIALRGDLALLKANFEANELFFISEDVIFKTYMSSPELLLTYMKINPLDQKTAEQQCGISDKILVLYCE
    GKLKIEQEKQNIRERLETSLKAYQSNIGGTASLIIASQTLVESLKNKNFIKGIRKLMLAHNKVFLNYLEE
    LDALERSLEQSKRQYLQERQSSKIIVK
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Oral therapeutic immunization with CFAdE plus polysaccharide adjuvant (PA) significantly decreased H. pylori colonization compared with oral immunization with urease plus PA, and the protection was correlated with IgG and sIgA antibody and antigen-specific CD4+ T cells (Guo et al., 2017).
4. flaA chimeric flagellin
  • Gene Name : flaA chimeric flagellin
  • Sequence Strain (Species/Organism) : Helicobacter pylori
  • NCBI Protein GI : AGI42755
  • Other Database IDs : CDD:237146
    CDD:279061
    CDD:284584
    CDD:279090
  • Taxonomy ID : 210
  • Gene Strand (Orientation) : ?
  • Protein Name : FlaA
  • Protein pI : 6.17
  • Protein Weight : 47725.66
  • Protein Length : 548
  • Protein Note : flagellin A; Reviewed
  • Protein Sequence : Show Sequence
    >AGI42755.1 FlaA, partial [Helicobacter pylori]
    NINAMNAHVQSALTQNALKTSLERLSSGLRINKAADDASGMTVADSLRSQASSLGQAIANTNDGMGIIQV
    ADKAMDEQLKILDTVKVKATQAAQDGQTTESRKAIQSDIVRLIQGLDNIGNTTTYNGQALLSGQFTNKEF
    QVGAYSNQSIKASIGSTTSDKIGQVRIATGALITASGDISLTFKQVDGVNDVTLESVKVSSSAGTGLGVL
    AEVINKNSNRTGVKAYASVITTSDVAVQSGSLSNLTLNGIHLGNIADIKKNDSDGRLVAAINAVTSETGV
    EAYTDQKGRLNLRSIDGRGIEIKTDSVSNGPSALTMVNGGQDLTKGSTNYGRLSLTRLDAKSINVVSASD
    SQHLGFTAIGFGESQVAETTVNLRDVTGNFNANVKSASGANYNAVIASGNQSLGSGVTTLRGAMVVIDIA
    ESAMKMLDKVRSDLGSVQNQMISTVNNISITQVNVKAAESQIRDVDFAEESANFNKNNILAQSGSYAMSQ
    A
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Vaccination with chimeric flagellin provided mice with significant protection against H. pylori (Mori et al., 2012).
5. ggt
  • Gene Name : ggt
  • Sequence Strain (Species/Organism) : Helicobacter pylori
  • NCBI Protein GI : ADN80237
  • Other Database IDs : CDD:129176
  • Taxonomy ID : 869727
  • Gene Strand (Orientation) : ?
  • Protein Name : Gamma-glutamyl transpeptidase
  • Protein pI : 9.66
  • Protein Weight : 57541.42
  • Protein Length : 645
  • Protein Note : gamma-glutamyltranspeptidase; TIGR00066
  • Protein Sequence : Show Sequence
    >ADN80237.1 Gamma-glutamyl transpeptidase [Helicobacter pylori 908]
    MRRSFLKTIGLGVIALSLGLLNPLSAASYPPIKNTKVGLALSSHPLATEIGQKVLEEGGNAIDAAVAIGF
    ALAVVHPAAGNIGGGGFAVIHLANGENVALDFREKAPLKATKNMFLDKQGNVVPKLSEDGYLAAGVPGTV
    AGMEAMLKKYGTKKLSQLIDPAIKLAENGYAISQRQAEILKEARERFLKYSSSKKYFFKKGHLDYQEGDL
    FVQKDLAKTLNQIKTLGAKGFYQGQVADLIEKDMQKNGGIITKEDLASYNVKWRKPVIGSYRGYKIISMS
    PPSSGGTHLIQILNVMENADLSALGYGASKNIHIVAEAMRQAYADRSVYMGDADFVSVPVDKLINKAYAK
    KIFDAIQPDTVTPSSQIKPGMGQLHEGSNTTHYSVADRWGNAVSVTYTINASYGSAASIDGAGFLLNNEM
    DDFSIKPGNPNLYGLVGGDANAIEANKRPLSSMSPTIVLKNNKVFLVVGSPGGSRIITTVLQVISNVIDY
    NMNISEAVSAPRFHMQWLPDELRIEKFGMPADVKDNLTKMGYQIVTKPVMGDVNAIQVLPKTKGSVFYGS
    TDPRKEF
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : The highest reduction in bacterial colonization was seen in mice immunized with the fusion protein rHspA-GGT when paired with the mucosal adjuvant LTB. Protection against H. pylori colonization was mediated by a strong systemic and localized humoral immune response (Zhang et al., 2015).
6. gltA
  • Gene Name : gltA
  • Sequence Strain (Species/Organism) : Helicobacter pylori
  • VO ID : VO_0012379
  • NCBI Protein GI : NP_206828
  • Other Database IDs : CDD:180164
    CDD:99867
  • Taxonomy ID : 85962
  • Gene Strand (Orientation) : ?
  • Protein Name : type II citrate synthase
  • Protein pI : 8.03
  • Protein Weight : 45749.59
  • Protein Length : 500
  • Protein Note : type II citrate synthase; Reviewed; PRK05614
  • Protein Sequence : Show Sequence
    >NP_206828.1 type II citrate synthase [Helicobacter pylori 26695]
    MSVTLVNNENNERYEFETIESTRGPKAVDFSKLFETTGFFSYDPGYSSTAGCQSKISYVNGKKGELYYRG
    HRIEDLVAKYKYVDVCKLLLTGELPKNQDESLEFELELRHRSFVHESLLNMFSAFPSNAHPMAKLSSGVS
    ILSTLYSTHQNMHTEEDYQTMARRIVAKIPTLAAICYRNEVGAPIIYPDIARSYVENILFMLRGYPYSRL
    KHTTQGEVEITPLEVEAFDKILTLHADHSQNASSTTVRNVASTGVHPYAAISAGISALWGHLHGGANEKV
    LLQLEEIGDVKNVDKYIARVKDKNDNFKLMGFGHRVYKSYDPRAKILKGLKDELHQKGVKMDERLSEIAA
    KVEEIALKDEYFIERNLYPNVDFYSGTILRALKIPVRFFTPVFVIGRTVGWCAQLLEHVKSPQARITRPR
    QVYVGD
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Mice were immunised with the citrate synthase protein by intra-Peyer's patch immunisation. Pre-immunisation with the citrate synthase protein led to a 84-91% reduction in H. pylori infection compared to unimmunised controls (Dunkley et al., 1999).
  • Related Vaccine(s): H. pylori GltA Protein Vaccine
7. hpaA
  • Gene Name : hpaA
  • Sequence Strain (Species/Organism) : Helicobacter pylori
  • NCBI Protein GI : WP_000855917
  • Other Database IDs : CDD:310078
  • Taxonomy ID : 210
  • Gene Strand (Orientation) : ?
  • Protein Name : neuraminyllactose-binding hemagglutinin
  • Protein pI : 8.62
  • Protein Weight : 28131.12
  • Protein Length : 343
  • Protein Note : Neuraminyllactose-binding hemagglutinin precursor (NLBH); pfam05211
  • Protein Sequence : Show Sequence
    >WP_000855917.1 neuraminyllactose-binding hemagglutinin [Helicobacter pylori]
    MKTNGHFKDFAWKKCFLGASVVALLVGCSPHIIETNEVALKLNYHPASEKVQALDEKILLLRPAFQYSDN
    IAKEYENKFKNQTTLKVEEILQNQGYKVINVDSSDKDDFSFAQKKEGYLAVAMNGEIVLRPDPKRTIQKK
    SEPGLLFSTGLDKMEGVLIPAGFVKVTILEPMSGESLDSFTMDLSELDIQEKFLKTTHSSHSGGLVSTMV
    KGTDNSNDAIKSALNKIFASIMQEMDKKLTQRNLESYQKDAKELKNKRNR
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Oral therapeutic immunization with CWAE significantly reduced the number of H. pylori colonies in the stomach of Mongolian gerbils, compared with oral immunization using CTB-UE or H. pylori urease. The protection of CWAE was associated with higher levels of mixed CD4+ T cell (Th cell) response, IgG, and secretory IgA (sIgA) antibodies to H. pylori (Guo et al., 2017).
8. hsp60
  • Gene Name : hsp60
  • Sequence Strain (Species/Organism) : Helicobacter pylori
  • VO ID : VO_0011336
  • NCBI Protein GI : 397869
  • Other Database IDs : CDD:234573
    CDD:239460
    GOA:P42383
    InterPro: IPR001844
    InterPro: IPR002423
    InterPro: IPR018370
    UniProtKB/UniProt: P42383
  • Taxonomy ID : 210
  • Gene Strand (Orientation) : ?
  • Protein Name : heat shock protein 60
  • Protein pI : 5.36
  • Protein Weight : 53991.72
  • Protein Length : 611
  • Protein Note : chaperonin GroEL; Reviewed; PRK00013
  • Protein Sequence : Show Sequence
    >CAA52062.1 heat shock protein 60 [Helicobacter pylori]
    MAKEIKFSDSARNLLFEGVRQLHDAVKVTMGPRGRNVLIQKSYGAPSITKDGVSVAKEIELSCPVANMGA
    QLVKEVASKTADAAGDGTTTATVLAYSIFKEGLRNITAGANPIEVKRGMDKAAEAIINELKKASKKVGGK
    EEITQVATISANSDHNIGKLIADAMEKVGKDGVITVEEAKGIEDELDVVEGMQFDRGYLSPYFVTNAEKM
    TAQLDNAYILLTDKKISSMKDILPLLEKTMKEGKPLLIIAEDIEGEALTTLVVNKLRGVLNIAAVKAPGF
    GDRRKEMLKDIAILTGGQVISEELGLSLENAEVEFLGKAGRIVIDKDNTTIVDGKGHSDDVKDRVAQIKT
    QIASTTSDYDKEKLQERLAKLSGGVAVIKVGAASEVEMKEKKDRVDDALSATKAAVEEGIVIGGGAALIR
    AAQKVHLNLHDDEKVGYEIIMRAIKAPLAQIAINAGYDGGVVVNEVEKHEGHFGFNASNGKYVDMFKEGI
    IDPLKVERIALQNAVSVSSLLLTTEATVHEIKEEKATPAMPDMGGMGGMGGMGGMM
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Researchers prepared an oral liposome-encapsulated recombinant Helicobacter pylori (Hp) heat shock protein 60 (Hsp60) vaccine and investigate its effect against Hp infection in mice. rHsp60 plus CT (choleratoxin), liposome-encapsulated rHsp60 and liposome-encapsulated rHsp60 plus CT had protective rates against Hp infection of 73.3%, 66.7% and 86.7%, respectively (Huang et al., 2005).

    Oral therapeutic immunization with CWAE significantly reduced the number of H. pylori colonies in the stomach of Mongolian gerbils, compared with oral immunization using CTB-UE or H. pylori urease. The protection of CWAE was associated with higher levels of mixed CD4+ T cell (Th cell) response, IgG, and secretory IgA (sIgA) antibodies to H. pylori (Guo et al., 2017).
9. hspA
  • Gene Name : hspA
  • Sequence Strain (Species/Organism) : Helicobacter pylori 85P
  • VO ID : VO_0012377
  • NCBI Protein GI : 712830
  • Other Database IDs : CDD:178988
    CDD:238197
  • Taxonomy ID : 210
  • Gene Strand (Orientation) : ?
  • Protein Name : heat shock protein
  • Protein pI : 6.66
  • Protein Weight : 12280.01
  • Protein Length : 174
  • Protein Note : co-chaperonin GroES; Reviewed; PRK00364
  • Protein Sequence : Show Sequence
    >AAC41440.1 heat shock protein [Helicobacter pylori]
    MKFQPLGERVLVERLEEENKTSSGIIIPDNAKEKPLMGVVKAVSHKISEGCKCVKEGDVIAFGKYKGAEI
    VLDGVEYMVLELEDILGIVGSGSCCHTGNHDHKHAKEHEACCHDHKKH
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Orogastric immunization of mice with recombinant H. pylori HspA proteins protected 80% of animals from a challenge dose of 10^4 Helicobacter felis bacteria (Ferrero et al., 1995).
    The highest reduction in bacterial colonization was seen in mice immunized with the fusion protein rHspA-GGT when paired with the mucosal adjuvant LTB. Protection against H. pylori colonization was mediated by a strong systemic and localized humoral immune response (Zhang et al., 2015).
  • Related Vaccine(s): H. pylori DNA vaccine pcDNA3.1-hspA , H. pylori HspA Protein Vaccine
10. hspB
  • Gene Name : hspB
  • Sequence Strain (Species/Organism) : Helicobacter pylori 85P
  • VO ID : VO_0012378
  • NCBI Protein GI : 712831
  • Other Database IDs : CDD:234573
    CDD:237231
    CDD:239460
  • Taxonomy ID : 210
  • Gene Strand (Orientation) : ?
  • Protein Name : heat shock protein
  • Protein pI : 5.47
  • Protein Weight : 53926.66
  • Protein Length : 607
  • Protein Note : chaperonin GroEL; Reviewed; PRK00013
  • Protein Sequence : Show Sequence
    >AAC41441.1 heat shock protein [Helicobacter pylori]
    MAKEIKFSDSARNLLFEGVRQLHDAVKVTMGPRGRNVLIQKSYGAPSITKDGVSVAKEIELSCPVANMGA
    QLVKEDASKTADAAGDGTTTATVLAYSIFKEGLRNITAGANPIEVKRGMDKAPEAIINELKKASKKVGGK
    EEITQVATISANSDHNIGKLIADAMEKVGKDGVITVEEAKGIEDELDVVEGMQFDRGYLSPYFVTNAEKM
    TAQLDNAYILLTDKKISSMKDILPLLEKTMKEGKPLLIIAEDIEGEALTTLVVNKLRGVLNIAAVKAPGF
    GDRRKEMLKDIAVLTGGQVISEELGLSLENAEVEFLGKAKIVIDKDNTTIVDGKGHSHDVKDRVAQIKTQ
    IASTTSDYDKEKLQERLAKLSGGVAVIKVGAASEVEMKEKKDRVDDALSATKAAVEEGIVIGGGAALIRA
    AQKVHLNLHDDEKVGYEIIMRAIKAPLAQIAINAGYDGGVVVNEVEKHEGHFGFNASNGKYVDMFKEGII
    DPLKVERIALQNAVSVSSLLLTTEATVHEIKEEKAAPAMPDMGGMGGMGGMGGMM
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Orogastric immunization of mice with recombinant H. pylori HspB proteins protected 70% of animals from a challenge dose of 10^4 Helicobacter felis bacteria (Ferrero et al., 1995).
  • Related Vaccine(s): H. pylori DNA vaccine pcDNA3.1-hspB , H. pylori HspB Protein Vaccine
11. katA
  • Gene Name : katA
  • Sequence Strain (Species/Organism) : Helicobacter pylori
  • VO ID : VO_0011339
  • NCBI Protein GI : WP_000247320
  • 3D structure: PDB ID : 1QWL
  • Other Database IDs : CDD:163712
  • Taxonomy ID : 210
  • Gene Strand (Orientation) : ?
  • Protein Name : catalase
  • Protein pI : 8.69
  • Protein Weight : 55672.85
  • Protein Length : 561
  • Protein Note : Clade 3 of the heme-binding enzyme catalase; cd08156
  • Protein Sequence : Show Sequence
    >WP_000247320.1 catalase [Helicobacter pylori]
    MVNKDVKQTTAFGAPVWDDNNVITAGPRGPVLLQSTWFLEKLAAFDRERIPERVVHAKGSGAYGTFTVTK
    DITKYTKAKIFSKVGKKTECFFRFSTVAGEKGSADAVRDPRGFAMKYYTEEGNWDLVGNNTPVFFIRDAI
    KFPDFIHTQKRDPQTNLPNPDMVWDFWSNVPESLYQVTWVMSDRGIPKSFRHMDGFGSHTFSLINAKGER
    FWVKFHFETMQGVKHLTNEEAAEVRKYDPDSNQRDLFDAIAGGDFPKWKMSIQVMPEEDAKKYRFHPFDV
    TKIWYLQDYPLMEVGIVELNKNPENYFAEVEQAAFTPANVVPGIGYSPDRMLQGRLFSYGDTHRYRLGVN
    YPQIPVNRPRCPFHSSSRDGYMQNGYYGSLQNYTPSSLPGYKEDKSARDPKFNLAHIEKEFEVWNWDYRA
    EDSDYYTQPGDYYRSLPADEKERLYDTIGGSLAHVTHKEIVDKQLEHFKKADPKYAEGVKKALEKHQKMM
    KDMHAKDMHHMKKKK
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Recombinant H. pylori catalase plus CT was used for immunization, and groups of mice were challenged with the Sydney strain of H. pylori. Immunization with recombinant catalase protected a significant proportion (9 of 10) of the mice from H. pylori challenge, indicating that this enzyme should be considered as a candidate for a future vaccine (Radcliff et al., 1997).

    Significant protection against H. pylori colonisation was induced with rSOD, rKatA and rTpx individually (Stent et al., 2012).
  • Related Vaccine(s): H. pylori catalase protein vaccine
12. lpp20
  • Gene Name : lpp20
  • Sequence Strain (Species/Organism) : Helicobacter pylori
  • NCBI Protein GI : AAA50860
  • Other Database IDs : CDD:280351
  • Taxonomy ID : 1111675
  • Protein Name : Lpp20 precursor
  • Protein pI : 10.15
  • Protein Weight : 17773.99
  • Protein Length : 235
  • Protein Note : LPP20 lipoprotein; pfam02169
  • Protein Sequence : Show Sequence
    >AAA50860.1 Lpp20 precursor [Helicobacter pylori 17874]
    MKNQVKKILGMSVVATMVIVGCSHAPKSGISKSNKAYKEATKGAPDWVVGDLEKVAKYEKYSGVFLGRAE
    DLITNNDVDYSTNQATAKARANLAANLKSTLQKDLENEKTRTVDASGKRSISGTDTEKISQLVDKELIAS
    KMLARYVGKDRGFVLVGLDKQIVDKVREELGMVKK
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : (Guo et al., 2017)
13. NAP
  • Gene Name : NAP
  • Sequence Strain (Species/Organism) : Helicobacter pylori
  • VO ID : VO_0011337
  • NCBI Protein GI : 8777456
  • 3D structure: PDB ID : 1JI4
  • Other Database IDs : CDD:223854
    CDD:153102
  • Taxonomy ID : 210
  • Gene Strand (Orientation) : ?
  • Protein Name : neutrophil-activating protein
  • Protein pI : 6.34
  • Protein Weight : 16292.55
  • Protein Length : 221
  • Protein Note : DNA-binding ferritin-like protein (oxidative damage protectant) [Inorganic ion transport and metabolism, Defense mechanisms]; COG0783
  • Protein Sequence : Show Sequence
    >BAA96880.1 neutrophil-activating protein, partial [Helicobacter pylori]
    MKTFEILKHLQADAIVLFMKVHNFHWNVKGTDFFNVHKATEEIYEGFADMFDDLAERIAQLGHHPLVTLS
    EALKLTRVKEETKTSFHSKDIFKEILEDYKHLEKEFKELSNTAEKEGDKVTVTYADDQLAKLQKSIWMLQ
    AHLA
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : A study shows that vaccination of mice with HP-NAP (H. pylori NAP) induces protection against H. pylori challenge, and that the majority of infected patients produce antibodies specific for HP-NAP, suggesting an important role of this factor in immunity (Satin et al., 2000).
    In this study, a multivalent epitope-based vaccine named CWAE against H. pylori urease, neutrophil-activating protein (NAP), heat shock protein 60 (HSP60) and H. pylori adhesin A (HpaA) was constructed based on mucosal adjuvant cholera toxin B subunit (CTB), Th1-type adjuvant NAP, multiple copies of selected B and Th cell epitopes and also the epitope-rich regions of urease B subunit The protection of CWAE was associated with higher levels of mixed CD4+ T cell (Th cell) response, IgG, and secretory IgA (sIgA) antibodies to H. pylori (Guo et al., 2017).
  • Related Vaccine(s): H. pylori NAP protein vaccine
14. oipA
  • Gene Name : oipA
  • Sequence Strain (Species/Organism) : Helicobacter pylori strain PD529
  • NCBI Protein GI : WP_000756902
  • Other Database IDs : CDD:280099
  • Taxonomy ID : 210
  • Gene Strand (Orientation) : ?
  • Protein Name : outer membrane protein
  • Protein pI : 10.05
  • Protein Weight : 33030.75
  • Protein Length : 374
  • Protein Note : Helicobacter outer membrane protein; pfam01856
  • Protein Sequence : Show Sequence
    >WP_000756902.1 outer membrane protein [Helicobacter pylori]
    MKKVLLLTLSLSLSFWLHAERNGFYLGLNFAEGSYIQGQGSIGEKASAENALNQAINNAKNSLFPNTKAI
    RDVQNALNAVKDSNKIANRFAGNGGSGGIFNELSLGYKYFLGKKRIIGFRHSLFFGYQLGGVGSVPGSGL
    IAFLPYGFNTDLLINWTNDKRASQEYVERRVKGLSIFYKDMTGRTLDADTLKRASRHIIRKSSGLVIGME
    LGASTWFASNNLTPFNQVKSRTIFQLQGKFGVRFSSDEYDIDRYGDENYLGGSSVELGVKVPAFKVNYYS
    DDYGDKLDYKRVVSVYLNYTYNFKNKH
  • Molecule Role : Protective antigen
  • Related Vaccine(s): H. pylori DNA vaccine poipA
15. outer membrane protein 26
  • Gene Name : outer membrane protein 26
  • Sequence Strain (Species/Organism) : Helicobacter pylori
  • NCBI Protein GI : AFX89461
  • Other Database IDs : CDD:280099
  • Taxonomy ID : 1055532
  • Gene Strand (Orientation) : ?
  • Protein Name : outer membrane protein 26
  • Protein pI : 10.25
  • Protein Weight : 50640.192
  • Protein Length : 548
  • Protein Note : clinical isolate from Inuvialuit
  • Protein Sequence : Show Sequence
    >AFX89461.1 outer membrane protein 26 [Helicobacter pylori Aklavik86]
    MKNTNTKEIENKRMKKGQYQTLKKGLLKTALLFSLPLSVALAEDDGFYMGIGYQIGGTQQSINNKGSTLR
    NNVINGFRQVGVGIAGDNGLLSVASNTMMNALLGIGKQILSDHVATTNNAQLTQFRDLLPQIEQRYQVDK
    NAYTIQALQLYLNDLLNNLVNNNNGSGSGSNPIGMGYATTIRTLSAAQTQFNLLATASVGLLNALTRVNV
    NSDSEFLRGLLGRMQLFNDTSSEELGKIGNNLSKSLAGIKLQDDVKAIQDRIDAYQGSLQQLKSSLNRYN
    EPYLPQFGPGKSSQHGVSNGIGIQMGYKQFFGGKRNVGLRYYAFFDYGFTQLGNLNSTINANIYTYGAGT
    DFLWNIFRRVFSDQSLHVGVFGGIQLAGTTWDSSLRKQIKNLFKKNPTPTNFQFLFNLGLRAHFSSTMHR
    RFLSASQSIQHGMEFGVKIPVINQRYLKANGADVDYRRLYAFYINYTIGF
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : We found that oral immunization of H. pylori-infected mice with rM. smegmatis-Omp26 induced protection, i.e., significant reduction in bacterial colonization in the stomach (et al., 2009).
16. tpx
  • Gene Name : tpx
  • Sequence Strain (Species/Organism) : Helicobacter pylori
  • NCBI Protein GI : ADZ50126
  • Other Database IDs : CDD:224988
    CDD:278975
    CDD:239312
  • Taxonomy ID : 985081
  • Protein Name : Thiol peroxidase
  • Protein pI : 5.81
  • Protein Weight : 17001.26
  • Protein Length : 226
  • Protein Note : Peroxiredoxin [Posttranslational modification, protein turnover, chaperones]; COG2077
  • Protein Sequence : Show Sequence
    >ADZ50126.1 Thiol peroxidase [Helicobacter pylori 2017]
    MQKVTFKEETYQLEGKALKVGDKAPDVKLVNGDLQEVNLLKQGVRFQVVSALPSLTGSVCLLQAKHFNEQ
    AGKLPSVSFSVISMDLPFSQGQICGAEGIKDLRILSDFRYKAFGENYGVLLGKGSLQGLLARSVFVLDDK
    GVVIYKEIVQNILEEPNYEALLEVLK
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : (Stent et al., 2012)
17. ureB
  • Gene Name : ureB
  • Sequence Strain (Species/Organism) : Helicobacter pylori
  • VO ID : VO_0011335
  • NCBI Protein GI : WP_000724295
  • Other Database IDs : CDD:184438
  • Taxonomy ID : 210
  • Gene Strand (Orientation) : ?
  • Protein Name : urease subunit alpha
  • Protein pI : 5.99
  • Protein Weight : 58828.9
  • Protein Length : 638
  • Protein Note : urease subunit beta; Provisional; PRK13985
  • Protein Sequence : Show Sequence
    >WP_000724295.1 urease subunit alpha [Helicobacter pylori]
    MKKISRKEYVSMYGPTTGDKVRLGDTDLIAEVEHDYTIYGEELKFGGGKTLREGMSQSNNPSKEELDLII
    TNALIVDYTGIYKADIGIKDGKIAGIGKGGNKDMQDGVKNNLSVGPATEALAGEGLIVTAGGIDTHIHFI
    SPQQIPTAFASGVTTMIGGGTGPADGTNATTITPGRRNLKWMLRAAEEYSMNLGFLAKGNASNDASLADQ
    IEAGAIGFKIHEDWGTTPSAINHALDVADKYDVQVAIHTDTLNEAGCVEDTMAAIAGRTMHTFHTEGAGG
    GHAPDIIKVAGEHNILPASTNPTIPFTVNTEAEHMDMLMVCHHLDKSIKEDVQFADSRIRPQTIAAEDTL
    HDMGIFSITSSDSQAMGRVGEVITRTWQTADKNKKEFGRLKEEKGDNDNFRIKRYLSKYTINPAIAHGIS
    EYVGSVEVGKVADLVLWSPAFFGVKPNMIIKGGFIALSQMGDANASIPTPQPVYYREMFAHHGKAKYDAN
    ITFVSQAAYDKGIKEELGLERQVLPVKNCRNITKKDMQFNDTTAHIEVNPETYHVFVDGKEVTSKPANKV
    SLAQLFSIF
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Vaccination with poliovirus vector containing the gene for the B subunit of H. pylori urease provides significant prophylactic and strong therapeutic protection against H. pylori in mice (Smythies et al., 2005).
  • Related Vaccine(s): H. pylori vaccine encoding UreB , SL3261- UreA and UreB
18. vacA
  • Gene Name : vacA
  • Sequence Strain (Species/Organism) : Helicobacter pylori
  • VO ID : VO_0011341
  • NCBI Protein GI : WP_123946465
  • Other Database IDs : CDD:111576
    CDD:309066
  • Taxonomy ID : 210
  • Gene Strand (Orientation) : ?
  • Protein Name : autotransporter vacuolating cytotoxin VacA
  • Protein pI : 9.4
  • Protein Weight : 132293.35
  • Protein Length : 1391
  • Protein Note : Vacuolating cyotoxin; pfam02691
  • Protein Sequence : Show Sequence
    >WP_123946465.1 autotransporter vacuolating cytotoxin VacA [Helicobacter pylori]
    MEIQQTHRKINRPLVSLVLAGALISAIPQQSHAAFFTTVIIPAIVGGIATGTAVGTVSGLLGWGLKQAEE
    ANKTPDKPDKVWRIQAGKGFNEFPNKEYDLYRSLLSSKIDGGWDWGNAATHYWVKGGQQNKLEVDMKDAV
    GTYKLSGLRNFTGGDLDVNMQKATLRLGQFNGNSFTSFKDSADRTTRVDFNAKNISIDNFVEINNRVGSG
    AGRKASSTVLTLQASEGITSSKNAEISLYDGATLNLASNSVKLNGNVWMGRLQYVGAYLAPSYSTINTSK
    VTGEVDFNHLTVGDKNAAQAGIIASNKTHIGTLDLWQSAGLNIIAPPEGGYKDKPKDKPSNTTQNNANNN
    QQNSAQNNSSTQVINPPNSAQKTEIQPTQVIDGPFAGGKDTVVNIDRINTKADGTIKVGGYKASLTTNAA
    HLHIGKGGVNLSNQASGRTLLVENLTGNITVDGPLRVNNQVGGYALAGSSANFEFKAGTDTKNGTATFNN
    DISLGRFVNLKVDAHTANFKGIDTGNGGFNTLDFSGVTGKVNINKLITASTNVAAKNFNINELIVKTNGV
    SVGEYTHFSEDIGSQSRINTVRLETGTRSIFSGGVKFKSGEKLVIDEFYYSPWNYFDARNIKNVEITRKF
    ASSTPENPWGTSKLMFNNLTLGQNAIMDYSQFSNLTIQGDFINNQGTINYLVRGGQVATLNVGNAAAMMF
    NNDIDSATGFYKPLIKINSAQDLIKNTEHVLLKAKIIGYGNVSTGTNGISNVNLEEQFKERLALYNNNNR
    MDTCVVRNTDDIKACGMAIGNQSMVNNPDNYKYLIGKAWKNIGISKTANGSKISVYYLGNSTPTENGGST
    TNLPTNTTNNARSANYALVKNAPFAHSATPNLVAINQHDFGTIESVFELANRSKDIDTLYTHSGAQGRDL
    LQTLLIDSHDAGYARTMIDATSANEITKQLNAATTTLNNIASLEHKTSGLQTLSLSNAMILNSRLVNLSR
    RHTNHIDSFAQRLQALKDQRFASLESAAEVLYQFAPKYEKPTNVWANAIGGASLNNGSNASLYGTSAGVD
    AFLNGNVEAIVGGFGSYGYSSFSNQANSLNSGANNANFGVYSRIFANQHEFDFEAQGALGSDQSSLNFKS
    ALLQDLNQSYNYLAYSATARASYGYDFAFFRNALVLKPSVGVGYNHLGSTNFKSNSQSQVALKNGASSQH
    LFNANANVEARYYYGDTSYFYMNAGVLQEFANFGSSNAVSLNTFKVNATHNPLNTHARVMMGGELKLAKE
    VFLNLGFVYLHNLISNIGHFASNLGMRYSF
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Treatment of the Helicobacter pylori vacuolating cytotoxin with very low concentrations of formaldehyde resulted in abrogation of toxic activity in both a HeLa cell vacuolation assay and an in vivo assay of gastric epithelial damage. Detoxification had only a minimal effect on the integrity of the oligomeric or monomeric structure. The toxoid retained the ability to bind to target cells and to induce high-titer neutralizing antibodies after immunization of rabbits. Furthermore, oral immunization of mice with the toxoid resulted in protection against infective challenge with mouse-adapted strains of H. pylori (Manetti et al., 1997).
  • Related Vaccine(s): H. pylori VacA protein vaccine
III. Vaccine Information
1. Epivac vaccine
a. Type:
Recombinant vector vaccine
b. Status:
Research
c. Host Species for Licensed Use:
Baboon
d. Host Species as Laboratory Animal Model:
Mice
e. Gene Engineering of cagA
  • Type: Recombinant protein preparation
  • Description: Compared to non-immunized mice, immunization with Epivac alone or with a Th1 adjuvant significantly reduced H. pylori colonization, and better protection was observed when an adjuvant was used (Li et al., 2012).
  • Detailed Gene Information: Click here.
f. Adjuvant:
  • VO ID: VO_0001237
  • Description: In six groups, mice (n = 10) were immunized three times at two-week intervals with PBS, Epivac or Epivac plus one of the following four Th1 adjuvants: CpG ODN 1826 (CpG, 20 μg/mouse, synthesized by Invitrogen), N-glycolyl-MDP VacciGrade (MDP, 30 μg/mouse, InvivoGen), MPLA VacciGrade (MPLA, 10 μg/mouse, InvivoGen) and Addavax (1:1, InvivoGen) (Li et al., 2012).
g. Immunization Route
subcutaneous injection
2. H. pylori AhpC vaccine
a. Type:
Recombinant vector vaccine
b. Status:
Research
c. Host Species for Licensed Use:
Baboon
d. Host Species as Laboratory Animal Model:
Mice
e. Immunization Route
subcutaneous injection
3. H. pylori catalase protein vaccine
a. Vaccine Ontology ID:
VO_0011513
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
H. pylori catalase
e. Gene Engineering of katA
  • Type: Recombinant protein preparation
  • Description: When required for use as a vaccine antigen, H. pylori was harvested from plates with 0.1 M phosphate-buffered saline (PBS), pelleted by centrifugation, and disrupted by sonication. The sonicate was stored at 220°C until use. Purified catalase was obtained by the method of Hazell et al. (11). Briefly, H. pylori cells were harvested with 0.1 M sodium phosphate buffer (pH 7.2), centrifuged, and then resuspended in the buffer. Cells were disrupted by sonication, cellular material was removed by centrifugation (5 min, 10,000 3 g), and then the supernatant was collected and filtered (0.22-mm-pore-size filter). Catalase was eluted by the creation of a gradient with 1 M NaCl in 0.01 M sodium phosphate buffer. The purified catalase was then filter sterilized, stored at 4°C, and protected from light (Radcliff et al., 1997).
  • Detailed Gene Information: Click here.
f. Adjuvant:
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Groups of mice were dosed orogastrically on days 0, 7, 14, and 21 with 200 mg of purified recombinant catalase plus 10 mg of CT, 1 mg of H. pylori 921023 sonicate plus 10 mg of CT, 1 mg of E. coli XLOLR sonicate plus 10 mg of CT, or PBS alone or were left unimmunized and unchallenged. One week after the last immunization dose, animals from the catalase plus CT and untreated groups were bled to obtain prechallenge sera (Radcliff et al., 1997).
  • Challenge Protocol: Two weeks after the last immunization dose, mice were challenged with three orogastric doses of live H. pylori SS1 cells (;107 organisms/dose) 2 days apart to ensure all animals were infected. After a further 2 weeks, the animals were killed and assessed for H. pylori infection (Radcliff et al., 1997).
  • Efficacy: Recombinant H. pylori catalase plus CT was used for immunization, and groups of mice were challenged with the Sydney strain of H. pylori. Immunization with recombinant catalase protected a significant proportion (9 of 10) of the mice from H. pylori challenge, indicating that this enzyme should be considered as a candidate for a future vaccine (Radcliff et al., 1997).
4. H. pylori CFAdE vaccine
a. Type:
Recombinant vector vaccine
b. Status:
Research
c. Host Species for Licensed Use:
Baboon
d. Host Species as Laboratory Animal Model:
Gerbils
e. Immunization Route
Oral
5. H. pylori DNA vaccine pcDNA3.1-hspA
a. Vaccine Ontology ID:
VO_0004560
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Antigen
HspA from H. pylori SS1 (Todoroki et al., 2000)
f. Gene Engineering of hspA
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
g. Vector:
pcDNA3.1 (Todoroki et al., 2000)
h. Immunization Route
Intracutaneous immunization
i. Mouse Response
  • Vaccine Immune Response Type: VO_0003057
  • Immune Response: Antibody isotypes were predominantly IgG2a (Th1-like) with pcDNA3.1-hspA (Todoroki et al., 2000).
  • Efficacy: The inflammation scores were significantly lower in pcDNA 3.1-hspA (46.5% reduction) immunized mice groups than in control group (100%). Colonization with H. pylori was verified histologically. There were a lot of bacteria colonies in the mucous layer of stomachs in all control group mice and fewer in HspA group mice (Todoroki et al., 2000).
6. H. pylori DNA vaccine pcDNA3.1-hspB
a. Vaccine Ontology ID:
VO_0004561
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Antigen
HspB from H. pylori SS1 (Todoroki et al., 2000)
f. Gene Engineering of hspB
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
g. Vector:
pcDNA3.1 (Todoroki et al., 2000)
h. Immunization Route
Intracutaneous immunization
i. Mouse Response
  • Vaccine Immune Response Type: VO_0003057
  • Immune Response: Antibody isotypes were predominantly mixed IgG1/IgG2a (Th0-like) with pcDNA3.1-hspB (Todoroki et al., 2000).
  • Efficacy: The inflammation scores were significantly lower in pcDNA 3.1-hspB (16.5% reduction) immunized mice groups than in control group (100%). Colonization with H. pylori was verified histologically. There were a lot of bacteria colonies in the mucous layer of stomachs in all control group mice and fewer in HspB group mice (Todoroki et al., 2000).
7. H. pylori DNA vaccine poipA
a. Vaccine Ontology ID:
VO_0004559
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Antigen
oipA from H. pylori SS1 (Chen et al., 2012)
f. Gene Engineering of oipA
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
g. Vector:
pVAX1 (Chen et al., 2012)
h. Immunization Route
Gene gun
i. Mouse Response
  • Vaccine Immune Response Type: VO_0003057
  • Immune Response: PoipA administered intradermally ('gene gun' immunization) promoted a strong Th2 immune response, whereas co-delivery of either pIL-2 or pLTB adjuvant elicited a Th1-biased immune response. PoipA administered with both pIL-2 and pLTB adjuvants promoted a strong Th1 immune response (Chen et al., 2012).
  • Efficacy: Mice immunized with poipA had significant drops in bacterial load in the stomach after challenge compared to the PBS and pVAX1 immunized control groups (P<0.001). In the groups in which poipA was co-administered with either pIL-2 or pLTB, the mice had almost a 2-log decrease in bacterial load compared to that of the controls (P<0.001). Mice in the groups in which poipA was co-administered with both pIL-2 and pLTB showed almost a 4-log decrease in bacterial load compared to that of the control groups (P<0.001) (Chen et al., 2012).
8. H. pylori GltA Protein Vaccine
a. Vaccine Ontology ID:
VO_0004062
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
Purified GltA protein
e. Gene Engineering of gltA
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
f. Adjuvant:
g. Immunization Route
intra-Peyer's patch (IPP)
h. Mouse Response
  • Host Strain: C57BL/6
  • Vaccination Protocol: Mice were immunised by the intra-Peyer's patch (IPP) route with purified GltA (at 0.5 mg protein ml−1) was contained in an homogenate of equal quantities of PBS and Freund's incomplete adjuvant. For IPP immunisation each mouse was anaesthetised by intraperitoneal injection of 200 μl of a ketamine, xylazine mixture made by mixing 10 ml of ketamine (100 μg ml−1) and 1 ml of xylazine (100 μg ml−1), the abdomen shaved and swabbed with 70% alcohol and a midline incision made in the skin and muscle layers to expose the intestine. Visible Peyer's patches were located along the length of the intestine and approximately 3 μl of homogenate injected directly under the serosa of each Peyer's patch (Dunkley et al., 1999).
  • Challenge Protocol: Mice were infected 2 weeks after immunisation with H. pylori Sydney strain 1 (SS1) (Dunkley et al., 1999).
  • Efficacy: Mice were immunised with the citrate synthase (GltA) protein by intra-Peyer's patch immunisation. Pre-immunisation with the citrate synthase protein led to a 84-91% reduction in H. pylori infection compared to unimmunised controls (Dunkley et al., 1999).
9. H. pylori HspA Protein Vaccine
a. Vaccine Ontology ID:
VO_0004060
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
Recombinant HspA protein
e. Gene Engineering of hspA
  • Type: Recombinant protein preparation
  • Description: The hspA gene was cloned into the expression vector pMAL-C2 and expressed in E. coli as a MalE fusion (Ferrero et al., 1995).
  • Detailed Gene Information: Click here.
f. Adjuvant:
  • VO ID: VO_0000143
  • Description: 5 μg of cholera toxin (Ferrero et al., 1995).
g. Immunization Route
Orally
h. Mouse Response
  • Host Strain: Swiss
  • Vaccination Protocol: Mice were orogastrically immunized with 50 μg of recombinant HspA protein and 5 μg of cholera toxin prepared in 0.1 M sodium bicarbonate before delivery (Ferrero et al., 1995).
  • Challenge Protocol: Mice were challenged with 10^4 H. felis bacteria (Ferrero et al., 1995).
  • Efficacy: Orogastric immunization of mice with recombinant H. pylori HspA proteins protected 80% of animals from a challenge dose of 10^4 Helicobacter felis bacteria (Ferrero et al., 1995).
i. Mouse Response
  • Host Strain: Swiss
  • Vaccination Protocol: Mice were orogastrically immunized with 50 μg of recombinant HspB protein and 5 μg of cholera toxin prepared in 0.1 M sodium bicarbonate before delivery (Ferrero et al., 1995).
  • Challenge Protocol: Mice were challenged with 10^4 H. felis bacteria (Ferrero et al., 1995).
  • Efficacy: Orogastric immunization of mice with recombinant H. pylori HspB proteins protected 70% of animals from a challenge dose of 104 Helicobacter felis bacteria (Ferrero et al., 1995).
10. H. pylori HspB Protein Vaccine
a. Vaccine Ontology ID:
VO_0004061
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
Recombinant HspB protein
e. Gene Engineering of hspB
  • Type: Recombinant protein preparation
  • Description: The hspB gene was cloned into the expression vector pMAL-C2 and expressed in E. coli as a MalE fusion
  • Detailed Gene Information: Click here.
f. Adjuvant:
  • VO ID: VO_0000143
  • Description: 5 μg of cholera toxin (Ferrero et al., 1995).
g. Immunization Route
Orally
h. Mouse Response
  • Host Strain: Swiss pathogen free
  • Vaccination Protocol: Antigen extracts (50 &mu;g of protein) containing 5 &mu;g of cholera toxin were used to immunize mice orogastrically (Ferrero et al., 1995).
  • Challenge Protocol: Aliquots (0.1 ml) containing 10^4 H. felis bacteria prepared from a low subculture stock suspension of H. felis were administered orogastrically to mice (Ferrero et al., 1995).
  • Efficacy: Orogastric immunization of mice with recombinant H. pylori HspB proteins protected 70% of animals from a challenge dose of 104 Helicobacter felis bacteria (Ferrero et al., 1995).
11. H. pylori NAP protein vaccine
a. Vaccine Ontology ID:
VO_0011514
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
H. pylori neutrophil-activating protein
e. Gene Engineering of NAP
  • Type: Recombinant protein preparation
  • Description: HP-NAP was cloned and expressed in Bacillus subtilis to avoid contamination with LPS. Two preparations of HP-NAP were isolated from H. pylori CCUG strain (Satin et al., 2000).
  • Detailed Gene Information: Click here.
f. Adjuvant:
g. Immunization Route
Intragastric
h. Mouse Response
  • Host Strain: CD-1
  • Vaccination Protocol: Groups of 10 mice (Charles River) were immunized intragastrically at days 0, 7, and 14 with saline alone (control) or with saline containing 100 mg of H. pylori CagA, glutathione S-transferase (GST)–HP-NAP, or H. pylori lysate together with 10 mg of LTK63 mutant as a mucosal adjuvant (Satin et al., 2000).
  • Challenge Protocol: At days 21, 23, and 25, all mice were challenged intragastrically with 10^9 CFU of H. pylori strain SPM326, a clinical isolate that has been adapted to colonize the mouse. At day 35, mice were killed, the stomachs were removed, and colonization was determined. Mice were considered as protected (not infected) when no H. pylori colony was detected on the stomach culture plates (Satin et al., 2000).
  • Efficacy: Study shows that vaccination of mice with HP-NAP induces protection against H. pylori challenge, and that the majority of infected patients produce antibodies specific for HP-NAP, suggesting an important role of this factor in immunity (Satin et al., 2000).
12. H. pylori VacA protein vaccine
a. Vaccine Ontology ID:
VO_0011479
b. Type:
Subunit vaccine
c. Status:
Research
d. Antigen
H. pylori vacuolating cytotoxin VacA
e. Gene Engineering of vacA
  • Type: Recombinant protein preparation
  • Description: VacA was purified from culture supernatant of H. pylori CCUG17874. Formaldehyde treatment was carried out by incubation of VacA (approximately 100 mg/ml) in a solution of phosphate-buffered saline (PBS) containing 25 mM lysine and 0.01% thimerosal (Sigma Chemicals, St. Louis, Mo.) plus different concentrations of formaldehyde for 48 h at 37°C followed by dialysis against PBS. Control VacA was treated in the same manner but in the absence of formaldehyde. VacA biological activity was assessed in a HeLa cell-vacuolating assay (14). Briefly, 104
    HeLa cells/well were seeded into 96-well flat-bottomed microtiter plates. After 16 h of incubation, the cells were treated for a further 8 h at 37°C with 2 mg of acid-activated VacA (2) in 100 ml of RPMI medium containing 2% fetal calf serum plus 5 mM ammonium chloride (Manetti et al., 1997).
  • Detailed Gene Information: Click here.
f. Adjuvant:
g. Immunization Route
Oral
h. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Groups of three 5-week-old male BALB/c mice were treated intragastrically with 5 mg of native or formaldehyde (3.2 mM)-treated VacA. The preparations were exposed to low pH in vitro in order to obtain optimal activation (Manetti et al., 1997).
  • Challenge Protocol: Mice were challenged with H. pylori
  • Efficacy: Treatment of the Helicobacter pylori vacuolating cytotoxin with very low concentrations of formaldehyde resulted in abrogation of toxic activity in both a HeLa cell vacuolation assay and an in vivo assay of gastric epithelial damage. Detoxification had only a minimal effect on the integrity of the oligomeric or monomeric structure. The toxoid retained the ability to bind to target cells and to induce high-titer neutralizing antibodies after immunization of rabbits. Furthermore, oral immunization of mice with the toxoid resulted in protection against infective challenge with mouse-adapted strains of H. pylori (Manetti et al., 1997).
13. H. pylori vaccine encoding UreB
a. Vaccine Ontology ID:
VO_0011477
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Antigen
H. pylori urease subunit B (ureB)
e. Gene Engineering of ureB
  • Type: Recombinant vector construction
  • Description: UreB replicon was constructed, encapsidated and produced as previously described in detail. Briefly, the plasmid pHP 902 containing the entire gene for the urease B subunit of a type 2 H. pylori (UMAB 41) was kindly provided by HL Mobley, University of Maryland. The urease gene was amplified by PCR using DNA primers with unique Xhol (5′) and HpaI (3′) restriction sites. The DNA product was cloned into the plasmid pCRII (Invirogen, San Diego, CA), digested with Xhol and HpaI, and ligated into a replicon cDNA. A schematic representation of the replicon encoding the B subunit of H. pylori urease (Smythies et al., 2005).
  • Detailed Gene Information: Click here.
f. Vector:
poliovirus
g. Immunization Route
Intramuscular injection (i.m.)
h. Mouse Response
  • Host Strain: C57BL/6/DAB
  • Vaccination Protocol: C57BL/6/DAB TgPVR mice were vaccinated intramuscularly with 107 infectious units of UreB replicon or control L1 replicon (5 mice each in Experiment 1 and 10 mice each in Experiment 2) and then boosted with UreB replicon or L1 replicon, respectively, 1 and 2 weeks later. Animals were immunized intramuscularly to assure delivery of equivalent amounts of vaccine to each animal and because poliovirus receptor transgenic mice are not susceptible to poliovirus infection by oral inoculation, even when the poliovirus receptor is overexpressed in the intestinal epithelium. Two weeks after the final boost, animals were inoculated with H. pylori SPM326 (150 μl, 109 CFU/ml) by oral gavage four times during a 10-day period with at least 3 days between each gavage (Smythies et al., 2005).
  • Challenge Protocol: Mice were challenged with H. pylori (Smythies et al., 2005).
  • Efficacy: Vaccination with poliovirus vector containing the gene for the B subunit of H. pylori urease provides significant prophylactic and strong therapeutic protection against H. pylori in mice (Smythies et al., 2005).
14. M. S- H. pylori -opm26
a. Vaccine Ontology ID:
VO_0004688
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Preparation
Recombinant Mycobacterium smegmatis expressing the H. pylori outer membrane protein 26-kilodalton (Omp26) antigen (et al., 2011).
f. Immunization Route
Intramuscular injection (i.m.)
g. Mouse Response
  • Vaccine Immune Response Type: VO_0003057
  • Efficacy: Six of the recombinant Mycobacterium-immunized mice (60%) were completely protected from H. pylori infection. The severity of H. pylori-associated chronic gastritis assessed histologically was significantly milder in mice vaccinated with recombinant Mycobacterium than in control animals (et al., 2011).
15. SL3261- UreA and UreB
a. Vaccine Ontology ID:
VO_0004675
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Gene Engineering of ureB
  • Type: Recombinant vector construction
  • Description: UreA and UreB, two structural subunits of the active enzyme, were expressed in the attenuated Salmonella typhimurium live vaccine SL3261 strain (Gómez-Duarte et al., 1998).
  • Detailed Gene Information: Click here.
f. Immunization Route
Intramuscular injection (i.m.)
g. Mouse Response
  • Vaccine Immune Response Type: VO_0003057
  • Immune Response: Oral immunization of mice with urease subunits delivered by an attenuated Salmonella strain induced a specific immune response (Gómez-Duarte et al., 1998).
  • Efficacy: Oral immunization of mice with urease subunits delivered by an attenuated Salmonella strain protected mice against H. pylori colonization (Gómez-Duarte et al., 1998).
IV. References
1. Chen et al., 2012: Chen J, Lin L, Li N, She F. Enhancement of Helicobacter pylori outer inflammatory protein DNA vaccine efficacy by co-delivery of interleukin-2 and B subunit heat-labile toxin gene encoded plasmids. Microbiology and immunology. 2012; 56(2); 85-92. [PubMed: 22150716].
2. Dunkley et al., 1999: Dunkley ML, Harris SJ, McCoy RJ, Musicka MJ, Eyers FM, Beagley LG, Lumley PJ, Beagley KW, Clancy RL. Protection against Helicobacter pylori infection by intestinal immunisation with a 50/52-kDa subunit protein. FEMS immunology and medical microbiology. 1999; 24(2); 221-225. [PubMed: 10378424].
3. Ferrero et al., 1995: Ferrero RL, Thiberge JM, Kansau I, Wuscher N, Huerre M, Labigne A. The GroES homolog of Helicobacter pylori confers protective immunity against mucosal infection in mice. Proceedings of the National Academy of Sciences of the United States of America. 1995; 92(14); 6499-6503. [PubMed: 7604021].
4. Gómez-Duarte et al., 1998: Gómez-Duarte OG, Lucas B, Yan ZX, Panthel K, Haas R, Meyer TF. Protection of mice against gastric colonization by Helicobacter pylori by single oral dose immunization with attenuated Salmonella typhimurium producing urease subunits A and B. Vaccine. 1998; 16(5); 460-471. [PubMed: 9491500].
5. Guo et al., 2017: Guo L, Yang H, Tang F, Yin R, Liu H, Gong X, Wei J, Zhang Y, Xu G, Liu K. Oral Immunization with a Multivalent Epitope-Based Vaccine, Based on NAP, Urease, HSP60, and HpaA, Provides Therapeutic Effect on <i>H. pylori</i> Infection in Mongolian gerbils. Frontiers in cellular and infection microbiology. 2017; 7; 349. [PubMed: 28824883].
6. Guo et al., 2017: Guo L, Yin R, Xu G, Gong X, Chang Z, Hong D, Liu H, Ding S, Han X, Li Y, Tang F, Liu K. Immunologic properties and therapeutic efficacy of a multivalent epitope-based vaccine against four Helicobacter pylori adhesins (urease, Lpp20, HpaA, and CagL) in Mongolian gerbils. Helicobacter. 2017; 22(6); . [PubMed: 28851031].
7. Huang et al., 2005: Huang W, Bai Y, Wang JD, Wu JB, Li GF, Zhang WM, Zhou DY. [Preparation oral liposome-encapsulated recombinant Helicobacter pylori heat shock protein 60 vaccine for prevention of Hp infection]. Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA. 2005; 25(5); 531-534. [PubMed: 15897126].
8. et al., 2011: Lü L, Zeng HQ, Wang PL, Shen W, Xiang TX, Mei ZC. Oral immunization with recombinant Mycobacterium smegmatis expressing the outer membrane protein 26-kilodalton antigen confers prophylactic protection against Helicobacter pylori infection. Clinical and vaccine immunology : CVI. 2011; 18(11); 1957-1961. [PubMed: 21900527].
9. Li et al., 2012: Li HB, Zhang JY, He YF, Chen L, Li B, Liu KY, Yang WC, Zhao Z, Zou QM, Wu C. Systemic immunization with an epitope-based vaccine elicits a Th1-biased response and provides protection against Helicobacter pylori in mice. Vaccine. 2012; 31(1); 120-126. [PubMed: 23137845].
10. Li et al., 2015: Li B, Chen L, Sun H, Yang W, Hu J, He Y, Wei S, Zhao Z, Zhang J, Li H, Zou Q, Wu C. Immunodominant epitope-specific Th1 but not Th17 responses mediate protection against Helicobacter pylori infection following UreB vaccination of BALB/c mice. Scientific reports. 2015; 5; 14793. [PubMed: 26434384].
11. Li et al., 2017: Li B, Yuan H, Chen L, Sun H, Hu J, Wei S, Zhao Z, Zou Q, Wu C. The influence of adjuvant on UreB protection against <i>Helicobacter pylori</i> through the diversity of CD4+ T-cell epitope repertoire. Oncotarget. 2017; 8(40); 68138-68152. [PubMed: 28978104].
12. Liu et al., 2004: Liu XL, Li SQ, Liu CJ, Tao HX, Zhang ZS. Antigen epitope of Helicobacter pylori vacuolating cytotoxin A. World journal of gastroenterology. 2004; 10(16); 2340-2343. [PubMed: 15285016].
13. L et al., 2009: L L, Cao HD, Zeng HQ, Wang PL, Wang LJ, Liu SN, Xiang TX. Recombinant Mycobacterium smegmatis mc(2)155 vaccine expressing outer membrane protein 26 kDa antigen affords therapeutic protection against Helicobacter pylori infection. Vaccine. 2009; 27(7); 972-978. [PubMed: 19111590].
14. Manetti et al., 1997: Manetti R, Massari P, Marchetti M, Magagnoli C, Nuti S, Lupetti P, Ghiara P, Rappuoli R, Telford JL. Detoxification of the Helicobacter pylori cytotoxin. Infection and immunity. 1997; 65(11); 4615-4619. [PubMed: 9353041].
15. Mori et al., 2012: Mori J, Vranac T, Smrekar B, Cernilec M, Serbec V?, Horvat S, Ihan A, Ben?ina M, Jerala R. Chimeric flagellin as the self-adjuvanting antigen for the activation of immune response against Helicobacter pylori. Vaccine. 2012; 30(40); 5856-5863. [PubMed: 22819990].
16. O'Riordan et al., 2012: O'Riordan AA, Morales VA, Mulligan L, Faheem N, Windle HJ, Kelleher DP. Alkyl hydroperoxide reductase: a candidate Helicobacter pylori vaccine. Vaccine. 2012; 30(26); 3876-3884. [PubMed: 22512976].
17. Radcliff et al., 1997: Radcliff FJ, Hazell SL, Kolesnikow T, Doidge C, Lee A. Catalase, a novel antigen for Helicobacter pylori vaccination. Infection and immunity. 1997; 65(11); 4668-4674. [PubMed: 9353048].
18. Salyers and Whitt., 2002: Abigail A. Salyers, Dixie D. Whitt. Helicobacter pylori, A Resourceful Gastric Pathogen. 339-49. Bacterial Pathogenesis: A Molecular Approach. 2002. ASM Press, Washington D.C. USA.
19. Satin et al., 2000: Satin B, Del Giudice G, Della Bianca V, Dusi S, Laudanna C, Tonello F, Kelleher D, Rappuoli R, Montecucco C, Rossi F. The neutrophil-activating protein (HP-NAP) of Helicobacter pylori is a protective antigen and a major virulence factor. The Journal of experimental medicine. 2000; 191(9); 1467-1476. [PubMed: 10790422].
20. Smythies et al., 2005: Smythies LE, Novak MJ, Waites KB, Lindsey JR, Morrow CD, Smith PD. Poliovirus replicons encoding the B subunit of Helicobacter pylori urease protect mice against H. pylori infection. Vaccine. 2005; 23(7); 901-909. [PubMed: 15603891].
21. Stent et al., 2012: Stent A, Every AL, Ng GZ, Chionh YT, Ong LS, Edwards SJ, Sutton P. Helicobacter pylori thiolperoxidase as a protective antigen in single- and multi-component vaccines. Vaccine. 2012; 30(50); 7214-7220. [PubMed: 23084846].
22. Todoroki et al., 2000: Todoroki I, Joh T, Watanabe K, Miyashita M, Seno K, Nomura T, Ohara H, Yokoyama Y, Tochikubo K, Itoh M. Suppressive effects of DNA vaccines encoding heat shock protein on Helicobacter pylori-induced gastritis in mice. Biochemical and biophysical research communications. 2000; 277(1); 159-163. [PubMed: 11027657].
23. Wiki: Helicobacter pylori: Helicobacter pylori [http://en.wikipedia.org/wiki/Helicobacter_pylori]
24. Zhang et al., 2015: Zhang X, Zhang J, Yang F, Wu W, Sun H, Xie Q, Si W, Zou Q, Yang Z. Immunization with Heat Shock Protein A and ?-Glutamyl Transpeptidase Induces Reduction on the Helicobacter pylori Colonization in Mice. PloS one. 2015; 10(6); e0130391. [PubMed: 26102080].