Helicobacter pylori 210 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). Ulcers 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). 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 hÄ›lix/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). Baboon Papio cynocephalus 9556 Bank vole Clethrionomys glareolus 447135 Bear Ursus americanus 9643 Birds Passeroidea 175121 Brown Trout Salmo trutta 8032 Buffalo Bison bison 9901 Carnivores Vulpes 9625 Cat Felis catus 9685 Catfishes Siluriformes 7995 Cattle Bos taurus 9913 Chicken Gallus gallus 9031 Chimpanzee Pan troglodytes 9598 chinchillas Chinchillidae 10150 Copper Pheasant Syrmaticus soemmerringii 9067 Deer Cervus elaphus 9860 Deer mouse Peromyscus maniculatus 10042 Dog Canis familiaris 9615 Ducks Anas 8835 Ferret Mustela putorius furo 9669 Fish Hyperotreti 117565 Gerbil Gerbillina 10045 Goat Capra hircus 9925 Gray wolf Canis lupus 9612 Guinea pig Cavia porcellus 10141 Hamster Mesocricetus auratus 10036 Horse Equus caballus 9796 Human Homo sapiens 9606 Macaque Macaca fascicularis 9541 Mongolian Gerbil Meriones unguiculatus 10047 Monkey Platyrrhini 9479 Mouse Mus musculus 10090 None None Parrot Psittacidae 9224 Pig Sus scrofa 9823 Rabbit Oryctolagus cuniculus 9986 Rainbow trout Oncorhynchus mykiss 8022 Rat Rattus 10114 Raven Corvus corax 56781 sei whale Balaenoptera borealis 9768 Sheep Ovis aries 9940 Squirrel Spermophilus richardsonii 37591 Tree shrew Tupaiidae 9393 Trouts, salmons & chars Salmoninae 504568 Turkey Meleagris gallopavo 9103 Vole Microtus ochrogaster 79684 Water buffalo Bubalus bubalis 391902 Epivac vaccine Recombinant vector vaccine Research subcutaneous injection Th1 adjuvant (Li et al., 2012). subcutaneous injection Recombinant protein preparation 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). H. pylori AhpC vaccine Recombinant vector vaccine Research subcutaneous injection 50% of mice immunized systemically with AhpC adjuvanted with alum (AhpC/alum) were shown to be protected from infection with H. pylori whereas 30% protection was observed for mice immunized systemically with AhpC alone (O'Riordan et al., 2012). subcutaneous injection H. pylori catalase protein vaccine VO_0011513 Subunit vaccine Research Cholera toxin (CT) H. pylori catalase Recombinant protein preparation 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). BALB/c 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). 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). 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). H. pylori CFAdE vaccine Recombinant vector vaccine Research Oral CTB (Cholera toxin B) (Guo et al., 2017). Oral H. pylori DNA vaccine pcDNA3.1-hspA VO_0004560 DNA vaccine Research pcDNA3.1 [Ref2682:Todoroki et al., 2000] Intracutaneous immunization Intracutaneous immunization HspA from H. pylori SS1 (Todoroki et al., 2000) DNA vaccine construction Antibody isotypes were predominantly IgG2a (Th1-like) with pcDNA3.1-hspA (Todoroki et al., 2000). VO_0003057 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). H. pylori DNA vaccine pcDNA3.1-hspB VO_0004561 DNA vaccine Research pcDNA3.1 [Ref2682:Todoroki et al., 2000] Intracutaneous immunization Intracutaneous immunization HspB from H. pylori SS1 (Todoroki et al., 2000) DNA vaccine construction Antibody isotypes were predominantly mixed IgG1/IgG2a (Th0-like) with pcDNA3.1-hspB (Todoroki et al., 2000). VO_0003057 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). H. pylori DNA vaccine poipA VO_0004559 DNA vaccine Research pVAX1 [Ref2681:Chen et al., 2012] Gene gun IL-2 or B subunit heat-labile toxin of Escherichia coli (Chen et al., 2012) Gene gun oipA from H. pylori SS1 (Chen et al., 2012) DNA vaccine construction 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). VO_0003057 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). H. pylori GltA Protein Vaccine VO_0004062 Subunit vaccine Research intra-Peyer's patch (IPP) Freund's incomplete adjuvant intra-Peyer's patch (IPP) Purified GltA protein Recombinant protein preparation C57BL/6 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). 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). Mice were infected 2 weeks after immunisation with H. pylori Sydney strain 1 (SS1) (Dunkley et al., 1999). H. pylori HspA Protein Vaccine VO_0004060 Subunit vaccine Research Orally 5 μg of cholera toxin (Ferrero et al., 1995). Orally Recombinant HspA protein Recombinant protein preparation The hspA gene was cloned into the expression vector pMAL-C2 and expressed in E. coli as a MalE fusion (Ferrero et al., 1995). Swiss 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). 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). Mice were challenged with 10^4 H. felis bacteria (Ferrero et al., 1995). Swiss 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). 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). Mice were challenged with 10^4 H. felis bacteria (Ferrero et al., 1995). H. pylori HspB Protein Vaccine VO_0004061 Subunit vaccine Research Orally 5 μg of cholera toxin (Ferrero et al., 1995). Orally Recombinant HspB protein Recombinant protein preparation The hspB gene was cloned into the expression vector pMAL-C2 and expressed in E. coli as a MalE fusion Swiss pathogen free Antigen extracts (50 &mu;g of protein) containing 5 &mu;g of cholera toxin were used to immunize mice orogastrically (Ferrero et al., 1995). 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). 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). H. pylori NAP protein vaccine VO_0011514 Subunit vaccine Research Intragastric LTK63 mutant of Escherichia coli heat-labile enterotoxin Intragastric H. pylori neutrophil-activating protein Recombinant protein preparation 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). CD-1 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). 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). 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). H. pylori VacA protein vaccine VO_0011479 Subunit vaccine Research Oral Aluminum hydroxide Oral H. pylori vacuolating cytotoxin VacA Recombinant protein preparation 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). BALB/c 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). 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). Mice were challenged with H. pylori H. pylori vaccine encoding UreB VO_0011477 Recombinant vector vaccine Research poliovirus Intramuscular injection (i.m.) Intramuscular injection (i.m.) H. pylori urease subunit B (ureB) Recombinant vector construction 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). C57BL/6/DAB 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). 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). Mice were challenged with H. pylori (Smythies et al., 2005). licensed Helicobacter pylori infection human vaccine Generic Unknown VO_0012181 Subunit vaccine Licensed A generic representation of vaccines utilized to prevent Helicobacter pylori infection in humans, typically composed of purified bacterial antigens such as urease or other H. pylori proteins. These subunit vaccines aim to induce protective immunity and reduce the risk of ulcers associated with H. pylori infection. M. S- H. pylori -opm26 VO_0004688 Recombinant vector vaccine Research Intramuscular injection (i.m.) Recombinant Mycobacterium smegmatis expressing the H. pylori outer membrane protein 26-kilodalton (Omp26) antigen (Lü et al., 2011). Intramuscular injection (i.m.) VO_0003057 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 (Lü et al., 2011). SL3261- UreA and UreB VO_0004675 Recombinant vector vaccine Research Intramuscular injection (i.m.) Intramuscular injection (i.m.) Recombinant vector construction 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). Oral immunization of mice with urease subunits delivered by an attenuated Salmonella strain induced a specific immune response (Gómez-Duarte et al., 1998). VO_0003057 Oral immunization of mice with urease subunits delivered by an attenuated Salmonella strain protected mice against H. pylori colonization (Gómez-Duarte et al., 1998). cagA Helicobacter pylori WP_130778457 CDD:302624 210 ? type IV secretion system oncogenic effector CagA 9.36 124904.51 1277 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 >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 Protective antigen 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 [Ref4797:Li et al., 2012]. gltA Helicobacter pylori VO_0012379 NP_206828 CDD:180164 CDD:99867 85962 ? type II citrate synthase 8.03 45749.59 500 type II citrate synthase; Reviewed; PRK05614 >NP_206828.1 type II citrate synthase [Helicobacter pylori 26695] MSVTLVNNENNERYEFETIESTRGPKAVDFSKLFETTGFFSYDPGYSSTAGCQSKISYVNGKKGELYYRG HRIEDLVAKYKYVDVCKLLLTGELPKNQDESLEFELELRHRSFVHESLLNMFSAFPSNAHPMAKLSSGVS ILSTLYSTHQNMHTEEDYQTMARRIVAKIPTLAAICYRNEVGAPIIYPDIARSYVENILFMLRGYPYSRL KHTTQGEVEITPLEVEAFDKILTLHADHSQNASSTTVRNVASTGVHPYAAISAGISALWGHLHGGANEKV LLQLEEIGDVKNVDKYIARVKDKNDNFKLMGFGHRVYKSYDPRAKILKGLKDELHQKGVKMDERLSEIAA KVEEIALKDEYFIERNLYPNVDFYSGTILRALKIPVRFFTPVFVIGRTVGWCAQLLEHVKSPQARITRPR QVYVGD Protective antigen 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 [Ref1487:Dunkley et al., 1999]. hspA Helicobacter pylori 85P VO_0012377 712830 CDD:178988 CDD:238197 210 ? heat shock protein 6.66 12280.01 174 co-chaperonin GroES; Reviewed; PRK00364 >AAC41440.1 heat shock protein [Helicobacter pylori] MKFQPLGERVLVERLEEENKTSSGIIIPDNAKEKPLMGVVKAVSHKISEGCKCVKEGDVIAFGKYKGAEI VLDGVEYMVLELEDILGIVGSGSCCHTGNHDHKHAKEHEACCHDHKKH Protective antigen Orogastric immunization of mice with recombinant H. pylori HspA proteins protected 80% of animals from a challenge dose of 10^4 Helicobacter felis bacteria [Ref1486: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 [Ref4749:Zhang et al., 2015]. hspB Helicobacter pylori 85P VO_0012378 712831 CDD:234573 CDD:237231 CDD:239460 210 ? heat shock protein 5.47 53926.66 607 chaperonin GroEL; Reviewed; PRK00013 >AAC41441.1 heat shock protein [Helicobacter pylori] MAKEIKFSDSARNLLFEGVRQLHDAVKVTMGPRGRNVLIQKSYGAPSITKDGVSVAKEIELSCPVANMGA QLVKEDASKTADAAGDGTTTATVLAYSIFKEGLRNITAGANPIEVKRGMDKAPEAIINELKKASKKVGGK EEITQVATISANSDHNIGKLIADAMEKVGKDGVITVEEAKGIEDELDVVEGMQFDRGYLSPYFVTNAEKM TAQLDNAYILLTDKKISSMKDILPLLEKTMKEGKPLLIIAEDIEGEALTTLVVNKLRGVLNIAAVKAPGF GDRRKEMLKDIAVLTGGQVISEELGLSLENAEVEFLGKAKIVIDKDNTTIVDGKGHSHDVKDRVAQIKTQ IASTTSDYDKEKLQERLAKLSGGVAVIKVGAASEVEMKEKKDRVDDALSATKAAVEEGIVIGGGAALIRA AQKVHLNLHDDEKVGYEIIMRAIKAPLAQIAINAGYDGGVVVNEVEKHEGHFGFNASNGKYVDMFKEGII DPLKVERIALQNAVSVSSLLLTTEATVHEIKEEKAAPAMPDMGGMGGMGGMGGMM Protective antigen Orogastric immunization of mice with recombinant H. pylori HspB proteins protected 70% of animals from a challenge dose of 10^4 Helicobacter felis bacteria [Ref1486:Ferrero et al., 1995]. katA Helicobacter pylori VO_0011339 WP_000247320 1QWL CDD:163712 210 ? catalase 8.69 55672.85 561 Clade 3 of the heme-binding enzyme catalase; cd08156 >WP_000247320.1 catalase [Helicobacter pylori] MVNKDVKQTTAFGAPVWDDNNVITAGPRGPVLLQSTWFLEKLAAFDRERIPERVVHAKGSGAYGTFTVTK DITKYTKAKIFSKVGKKTECFFRFSTVAGEKGSADAVRDPRGFAMKYYTEEGNWDLVGNNTPVFFIRDAI KFPDFIHTQKRDPQTNLPNPDMVWDFWSNVPESLYQVTWVMSDRGIPKSFRHMDGFGSHTFSLINAKGER FWVKFHFETMQGVKHLTNEEAAEVRKYDPDSNQRDLFDAIAGGDFPKWKMSIQVMPEEDAKKYRFHPFDV TKIWYLQDYPLMEVGIVELNKNPENYFAEVEQAAFTPANVVPGIGYSPDRMLQGRLFSYGDTHRYRLGVN YPQIPVNRPRCPFHSSSRDGYMQNGYYGSLQNYTPSSLPGYKEDKSARDPKFNLAHIEKEFEVWNWDYRA EDSDYYTQPGDYYRSLPADEKERLYDTIGGSLAHVTHKEIVDKQLEHFKKADPKYAEGVKKALEKHQKMM KDMHAKDMHHMKKKK Protective antigen 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 [Ref1399:Radcliff et al., 1997]. Significant protection against H. pylori colonisation was induced with rSOD, rKatA and rTpx individually [Ref4856:Stent et al., 2012]. NAP Helicobacter pylori VO_0011337 8777456 1JI4 CDD:223854 CDD:153102 210 ? neutrophil-activating protein 6.34 16292.55 221 DNA-binding ferritin-like protein (oxidative damage protectant) [Inorganic ion transport and metabolism, Defense mechanisms]; COG0783 >BAA96880.1 neutrophil-activating protein, partial [Helicobacter pylori] MKTFEILKHLQADAIVLFMKVHNFHWNVKGTDFFNVHKATEEIYEGFADMFDDLAERIAQLGHHPLVTLS EALKLTRVKEETKTSFHSKDIFKEILEDYKHLEKEFKELSNTAEKEGDKVTVTYADDQLAKLQKSIWMLQ AHLA Protective antigen 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 [Ref1397: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 [Ref4782:Guo et al., 2017]. oipA Helicobacter pylori strain PD529 WP_000756902 CDD:280099 210 ? outer membrane protein 10.05 33030.75 374 Helicobacter outer membrane protein; pfam01856 >WP_000756902.1 outer membrane protein [Helicobacter pylori] MKKVLLLTLSLSLSFWLHAERNGFYLGLNFAEGSYIQGQGSIGEKASAENALNQAINNAKNSLFPNTKAI RDVQNALNAVKDSNKIANRFAGNGGSGGIFNELSLGYKYFLGKKRIIGFRHSLFFGYQLGGVGSVPGSGL IAFLPYGFNTDLLINWTNDKRASQEYVERRVKGLSIFYKDMTGRTLDADTLKRASRHIIRKSSGLVIGME LGASTWFASNNLTPFNQVKSRTIFQLQGKFGVRFSSDEYDIDRYGDENYLGGSSVELGVKVPAFKVNYYS DDYGDKLDYKRVVSVYLNYTYNFKNKH Protective antigen ureB Helicobacter pylori VO_0011335 WP_000724295 CDD:184438 210 ? urease subunit alpha 5.99 58828.9 638 urease subunit beta; Provisional; PRK13985 >WP_000724295.1 urease subunit alpha [Helicobacter pylori] MKKISRKEYVSMYGPTTGDKVRLGDTDLIAEVEHDYTIYGEELKFGGGKTLREGMSQSNNPSKEELDLII TNALIVDYTGIYKADIGIKDGKIAGIGKGGNKDMQDGVKNNLSVGPATEALAGEGLIVTAGGIDTHIHFI SPQQIPTAFASGVTTMIGGGTGPADGTNATTITPGRRNLKWMLRAAEEYSMNLGFLAKGNASNDASLADQ IEAGAIGFKIHEDWGTTPSAINHALDVADKYDVQVAIHTDTLNEAGCVEDTMAAIAGRTMHTFHTEGAGG GHAPDIIKVAGEHNILPASTNPTIPFTVNTEAEHMDMLMVCHHLDKSIKEDVQFADSRIRPQTIAAEDTL HDMGIFSITSSDSQAMGRVGEVITRTWQTADKNKKEFGRLKEEKGDNDNFRIKRYLSKYTINPAIAHGIS EYVGSVEVGKVADLVLWSPAFFGVKPNMIIKGGFIALSQMGDANASIPTPQPVYYREMFAHHGKAKYDAN ITFVSQAAYDKGIKEELGLERQVLPVKNCRNITKKDMQFNDTTAHIEVNPETYHVFVDGKEVTSKPANKV SLAQLFSIF Protective antigen 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 [Ref1395:Smythies et al., 2005]. vacA Helicobacter pylori VO_0011341 WP_123946465 CDD:111576 CDD:309066 210 ? autotransporter vacuolating cytotoxin VacA 9.4 132293.35 1391 Vacuolating cyotoxin; pfam02691 >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 Protective antigen 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 [Ref1401:Manetti et al., 1997]. Chen et al., 2012 journal Chen J, Lin L, Li N, She F 2012 56 2 85-92 Microbiology and immunology Dunkley et al., 1999 journal Dunkley ML, Harris SJ, McCoy RJ, Musicka MJ, Eyers FM, Beagley LG, Lumley PJ, Beagley KW, Clancy RL 1999 24 2 221-225 FEMS immunology and medical microbiology Ferrero et al., 1995 journal Ferrero RL, Thiberge JM, Kansau I, Wuscher N, Huerre M, Labigne A 1995 92 14 6499-6503 Proceedings of the National Academy of Sciences of the United States of America Gómez-Duarte et al., 1998 journal Gómez-Duarte OG, Lucas B, Yan ZX, Panthel K, Haas R, Meyer TF 1998 16 5 460-471 Vaccine Guo et al., 2017 journal Guo L, Yin R, Xu G, Gong X, Chang Z, Hong D, Liu H, Ding S, Han X, Li Y, Tang F, Liu K 2017 22 6 Helicobacter Guo et al., 2017 journal Guo L, Yang H, Tang F, Yin R, Liu H, Gong X, Wei J, Zhang Y, Xu G, Liu K 2017 7 349 Frontiers in cellular and infection microbiology Huang et al., 2005 journal Huang W, Bai Y, Wang JD, Wu JB, Li GF, Zhang WM, Zhou DY 2005 25 5 531-534 Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA Lü et al., 2011 journal Lü L, Zeng HQ, Wang PL, Shen W, Xiang TX, Mei ZC 2011 18 11 1957-1961 Clinical and vaccine immunology : CVI Li et al., 2012 journal Li HB, Zhang JY, He YF, Chen L, Li B, Liu KY, Yang WC, Zhao Z, Zou QM, Wu C 2012 31 1 120-126 Vaccine Li et al., 2015 journal Li B, Chen L, Sun H, Yang W, Hu J, He Y, Wei S, Zhao Z, Zhang J, Li H, Zou Q, Wu C 2015 5 14793 Scientific reports Li et al., 2017 journal Li B, Yuan H, Chen L, Sun H, Hu J, Wei S, Zhao Z, Zou Q, Wu C 2017 8 40 68138-68152 Oncotarget Liu et al., 2004 journal Liu XL, Li SQ, Liu CJ, Tao HX, Zhang ZS 2004 10 16 2340-2343 World journal of gastroenterology Lü et al., 2009 journal Lü L, Cao HD, Zeng HQ, Wang PL, Wang LJ, Liu SN, Xiang TX 2009 27 7 972-978 Vaccine Manetti et al., 1997 journal Manetti R, Massari P, Marchetti M, Magagnoli C, Nuti S, Lupetti P, Ghiara P, Rappuoli R, Telford JL 1997 65 11 4615-4619 Infection and immunity Mori et al., 2012 journal Mori J, Vranac T, Smrekar B, Cernilec M, Serbec VČ, Horvat S, Ihan A, Benčina M, Jerala R 2012 30 40 5856-5863 Vaccine O'Riordan et al., 2012 journal O'Riordan AA, Morales VA, Mulligan L, Faheem N, Windle HJ, Kelleher DP 2012 30 26 3876-3884 Vaccine Radcliff et al., 1997 journal Radcliff FJ, Hazell SL, Kolesnikow T, Doidge C, Lee A 1997 65 11 4668-4674 Infection and immunity Salyers and Whitt., 2002 book Abigail A. Salyers, Dixie D. Whitt 2002 339-49 Bacterial Pathogenesis: A Molecular Approach ASM Press Washington D.C. USA 1-55581-171-x Satin et al., 2000 journal Satin B, Del Giudice G, Della Bianca V, Dusi S, Laudanna C, Tonello F, Kelleher D, Rappuoli R, Montecucco C, Rossi F 2000 191 9 1467-1476 The Journal of experimental medicine Smythies et al., 2005 journal Smythies LE, Novak MJ, Waites KB, Lindsey JR, Morrow CD, Smith PD 2005 23 7 901-909 Vaccine Stent et al., 2012 journal Stent A, Every AL, Ng GZ, Chionh YT, Ong LS, Edwards SJ, Sutton P 2012 30 50 7214-7220 Vaccine Todoroki et al., 2000 journal Todoroki I, Joh T, Watanabe K, Miyashita M, Seno K, Nomura T, Ohara H, Yokoyama Y, Tochikubo K, Itoh M 2000 277 1 159-163 Biochemical and biophysical research communications Wiki: Helicobacter pylori website http://en.wikipedia.org/wiki/Helicobacter_pylori Zhang et al., 2015 journal Zhang X, Zhang J, Yang F, Wu W, Sun H, Xie Q, Si W, Zou Q, Yang Z 2015 10 6 e0130391 PloS one