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Vaccine Comparison

H. pylori catalase protein vaccine H. pylori DNA vaccine pcDNA3.1-hspA H. pylori DNA vaccine pcDNA3.1-hspB H. pylori DNA vaccine poipA H. pylori GltA Protein Vaccine H. pylori HspA Protein Vaccine H. pylori HspB Protein Vaccine H. pylori NAP protein vaccine H. pylori VacA protein vaccine H. pylori vaccine encoding UreB M. S- H. pylori -opm26 SL3261- UreA and UreB
Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information
  • Vaccine Ontology ID: VO_0011513
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: H. pylori catalase
  • katA gene engineering:
    • 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.
  • Adjuvant: cholera toxin
  • Vaccine Ontology ID: VO_0004560
  • Type: DNA vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Mouse
  • Antigen: HspA from H. pylori SS1 (Todoroki et al., 2000)
  • hspA gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • Vector: pcDNA3.1 (Todoroki et al., 2000)
  • Immunization Route: Intracutaneous immunization
  • Vaccine Ontology ID: VO_0004561
  • Type: DNA vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Mouse
  • Antigen: HspB from H. pylori SS1 (Todoroki et al., 2000)
  • hspB gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • Vector: pcDNA3.1 (Todoroki et al., 2000)
  • Immunization Route: Intracutaneous immunization
  • Vaccine Ontology ID: VO_0004559
  • Type: DNA vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Mouse
  • Antigen: oipA from H. pylori SS1 (Chen et al., 2012)
  • oipA gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • Vector: pVAX1 (Chen et al., 2012)
  • Immunization Route: Gene gun
  • Vaccine Ontology ID: VO_0004062
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: Purified GltA protein
  • gltA gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Adjuvant: incomplete Freunds adjuvant
  • Immunization Route: intra-Peyer's patch (IPP)
  • Vaccine Ontology ID: VO_0004060
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: Recombinant HspA protein
  • hspA gene engineering:
    • 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.
  • Adjuvant: cholera toxin
    • VO ID: VO_0000143
    • Description: 5 μg of cholera toxin (Ferrero et al., 1995).
  • Immunization Route: Orally
  • Vaccine Ontology ID: VO_0004061
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: Recombinant HspB protein
  • hspB gene engineering:
    • 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.
  • Adjuvant: cholera toxin
    • VO ID: VO_0000143
    • Description: 5 μg of cholera toxin (Ferrero et al., 1995).
  • Immunization Route: Orally
  • Vaccine Ontology ID: VO_0011514
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: H. pylori neutrophil-activating protein
  • NAP gene engineering:
    • 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.
  • Adjuvant: LTK63 vaccine mutant
  • Immunization Route: Intragastric
  • Vaccine Ontology ID: VO_0011479
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: H. pylori vacuolating cytotoxin VacA
  • vacA gene engineering:
    • 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.
  • Adjuvant: aluminum hydroxide vaccine adjuvant
  • Immunization Route: Oral
  • Vaccine Ontology ID: VO_0011477
  • Type: Recombinant vector vaccine
  • Status: Research
  • Antigen: H. pylori urease subunit B (ureB)
  • ureB gene engineering:
    • 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.
  • Vector: poliovirus
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0004688
  • Type: Recombinant vector vaccine
  • Status: Research
  • Host Species for Licensed Use: Baboon
  • Preparation: Recombinant Mycobacterium smegmatis expressing the H. pylori outer membrane protein 26-kilodalton (Omp26) antigen (et al., 2011).
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0004675
  • Type: Recombinant vector vaccine
  • Status: Research
  • Host Species for Licensed Use: Baboon
  • ureB gene engineering:
    • 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.
  • Immunization Route: Intramuscular injection (i.m.)
Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response

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).

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).

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).

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).

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).

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 104 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 104 Helicobacter felis bacteria (Ferrero et al., 1995).

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 104 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).

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 104 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).

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 109 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).

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).

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).

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).

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).
References References References References References References References References References References References References
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].