{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:35:10Z","timestamp":1791930910230,"version":"4.3.4"},"reference-count":87,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MacKay Memorial Hospital (MMH)-National Tsing Hua University (NTHU) Joint Research","award":["111Q2504E1"],"award-info":[{"award-number":["111Q2504E1"]}]},{"name":"MacKay Memorial Hospital (MMH)-National Tsing Hua University (NTHU) Joint Research","award":["MOST110-2311-B-007-002"],"award-info":[{"award-number":["MOST110-2311-B-007-002"]}]},{"DOI":"10.13039\/501100004663","name":"National Science and Technology Council of Taiwan","doi-asserted-by":"publisher","award":["111Q2504E1"],"award-info":[{"award-number":["111Q2504E1"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"National Science and Technology Council of Taiwan","doi-asserted-by":"publisher","award":["MOST110-2311-B-007-002"],"award-info":[{"award-number":["MOST110-2311-B-007-002"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NTHU President\u2019s Scholarship","award":["111Q2504E1"],"award-info":[{"award-number":["111Q2504E1"]}]},{"name":"NTHU President\u2019s Scholarship","award":["MOST110-2311-B-007-002"],"award-info":[{"award-number":["MOST110-2311-B-007-002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Helicobacter pylori neutrophil-activating protein (HP-NAP), a major virulence factor of H. pylori, plays a role in bacterial protection and host inflammation. HP-NAP activates a variety of innate immune cells, including neutrophils, monocytes, and mast cells, to induce their pro-oxidant and pro-inflammatory activities. This protein also induces T-helper type 1 (Th1) immune response and cytotoxic T lymphocyte (CTL) activity, supporting that HP-NAP is able to promote gastric inflammation by activation of adaptive immune responses. Thus, HP-NAP is a potential therapeutic target for the treatment of H. pylori-induced gastric inflammation. The inflammatory responses triggered by HP-NAP are mediated by a PTX-sensitive G protein-coupled receptor and Toll-like receptor 2. Drugs designed to block the interactions between HP-NAP and its receptors could alleviate the inflammation in gastric mucosa caused by H. pylori infection. In addition, HP-NAP acts as a promising therapeutic agent for vaccine development, allergy treatment, and cancer immunotherapy. The high antigenicity of HP-NAP makes this protein a component of vaccines against H. pylori infection. Due to its immunomodulatory activity to stimulate the Th1-inducing ability of dendritic cells, enhance Th1 immune response and CTL activity, and suppress Th2-mediated allergic responses, HP-NAP could also act as an adjuvant in vaccines, a drug candidate against allergic diseases, and an immunotherapeutic agent for cancer. This review highlights the role of HP-NAP in the pathogenesis of H. pylori and the potential for this protein to be a therapeutic target in the treatment of H. pylori infection and therapeutic agents against H. pylori-associated diseases, allergies, and cancer.<\/jats:p>","DOI":"10.3390\/ijms24010091","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T06:11:24Z","timestamp":1671603084000},"page":"91","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["The Role of Helicobacter pylori Neutrophil-Activating Protein in the Pathogenesis of H. pylori and Beyond: From a Virulence Factor to Therapeutic Targets and Therapeutic Agents"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6346-2785","authenticated-orcid":false,"given":"Hua-Wen","family":"Fu","sequence":"first","affiliation":[{"name":"Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 30013, Taiwan"},{"name":"Department of Life Science, National Tsing Hua University, Hsinchu 30013, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chang","family":"Lai","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 30013, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1128\/CMR.00054-05","article-title":"Pathogenesis of Helicobacter pylori infection","volume":"19","author":"Kusters","year":"2006","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","first-page":"1273","article-title":"Unidentified curved bacilli on gastric epithelium in active chronic gastritis","volume":"1","author":"Warren","year":"1983","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/S0140-6736(84)91816-6","article-title":"Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration","volume":"1","author":"Marshall","year":"1984","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1053\/j.gastro.2017.04.022","article-title":"Global prevalence of Helicobacter pylori infection: Systematic review and meta-analysis","volume":"153","author":"Hooi","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1534\/genetics.115.176404","article-title":"Worldwide population structure, long-term demography, and local adaptation of Helicobacter pylori","volume":"200","author":"Montano","year":"2015","journal-title":"Genetics"},{"key":"ref_6","unstructured":"International Agency for Research on Cancer (1994). IARC monographs on the evaluation of the carcinogenic risks to humans. Schistosomes, Liver Flukes and Helicobacter pylori, International Agency for Research on Cancer."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3322\/canjclin.55.2.74","article-title":"Global cancer statistics, 2002","volume":"55","author":"Parkin","year":"2005","journal-title":"CA Cancer J. Clin."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/ijc.28999","article-title":"Global burden of gastric cancer attributable to Helicobacter pylori","volume":"136","author":"Plummer","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/S1438-4221(01)80002-3","article-title":"Virulence factors of Helicobacter pylori","volume":"290","author":"Dundon","year":"2001","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.4137\/CGast.S13760","article-title":"Virulence factors of Helicobacter pylori: A review","volume":"7","author":"Roesler","year":"2014","journal-title":"Clin. Med. Insights Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Baj, J., Forma, A., Sitarz, M., Portincasa, P., Garruti, G., Krasowska, D., and Maciejewski, R. (2020). Helicobacter pylori virulence factors-mechanisms of bacterial pathogenicity in the gastric microenvironment. Cells, 10.","DOI":"10.3390\/cells10010027"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1128\/iai.63.6.2213-2220.1995","article-title":"Characterization of a Helicobacter pylori neutrophil-activating protein","volume":"63","author":"Evans","year":"1995","journal-title":"Infect. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0022-2836(02)00879-3","article-title":"Structure of the neutrophil-activating protein from Helicobacter pylori","volume":"323","author":"Zanotti","year":"2002","journal-title":"J. Mol. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1046\/j.1365-2958.1999.01584.x","article-title":"The Helicobacter pylori neutrophil-activating protein is an iron-binding protein with dodecameric structure","volume":"34","author":"Tonello","year":"1999","journal-title":"Mol. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0378-1119(94)00774-M","article-title":"Identification of four new prokaryotic bacterioferritins, from Helicobacter pylori, Anabaena variabilis, Bacillus subtilis and Treponema pallidum, by analysis of gene sequences","volume":"153","author":"Evans","year":"1995","journal-title":"Gene"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/nsb0498-294","article-title":"The crystal structure of Dps, a ferritin homolog that binds and protects DNA","volume":"5","author":"Grant","year":"1998","journal-title":"Nat. Struct. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1111\/j.1742-4658.2007.06201.x","article-title":"Helicobacter pylori neutrophil-activating protein activates neutrophils by its C-terminal region even without dodecamer formation, which is a prerequisite for DNA protection\u2014novel approaches against Helicobacter pylori inflammation","volume":"275","author":"Kottakis","year":"2008","journal-title":"FEBS J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1099\/jmm.0.05070-0","article-title":"NapA protects Helicobacter pylori from oxidative stress damage, and its production is influenced by the ferric uptake regulator","volume":"52","author":"Cooksley","year":"2003","journal-title":"J. Med. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6839","DOI":"10.1128\/IAI.00991-06","article-title":"Dual Roles of Helicobacter pylori NapA in inducing and combating oxidative stress","volume":"74","author":"Wang","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1093\/nar\/gkm077","article-title":"The neutrophil-activating Dps protein of Helicobacter pylori, HP-NAP, adopts a mechanism different from Escherichia coli Dps to bind and condense DNA","volume":"35","author":"Ceci","year":"2007","journal-title":"Nucleic. Acids. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5294","DOI":"10.3748\/wjg.v20.i18.5294","article-title":"Helicobacter pylori neutrophil-activating protein: From molecular pathogenesis to clinical applications","volume":"20","author":"Fu","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1084\/jem.191.9.1467","article-title":"The neutrophil-activating protein (HP-NAP) of Helicobacter pylori is a protective antigen and a major virulence factor","volume":"191","author":"Satin","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.toxicon.2009.09.020","article-title":"The immune modulating activity of the Helicobacter pylori HP-NAP: Friend or foe?","volume":"56","year":"2010","journal-title":"Toxicon"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e00152-21","DOI":"10.1128\/AAC.00152-21","article-title":"SpoT-mediated NapA upregulation promotes oxidative stress-induced Helicobacter pylori biofilm formation and confers multidrug resistance","volume":"65","author":"Zhao","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1523-5378.2010.00815.x","article-title":"Proteomannans in biofilm of Helicobacter pylori ATCC 43504","volume":"16","author":"Yang","year":"2011","journal-title":"Helicobacter"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.4049\/jimmunol.178.3.1312","article-title":"The neutrophil-activating protein of Helicobacter pylori crosses endothelia to promote neutrophil adhesion in vivo","volume":"178","author":"Polenghi","year":"2007","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.femsle.2005.06.008","article-title":"Helicobacter pylori induce neutrophil transendothelial migration: Role of the bacterial HP-NAP","volume":"249","author":"Brisslert","year":"2005","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.bbrc.2008.09.072","article-title":"Helicobacter pylori neutrophil-activating protein promotes myeloperoxidase release from human neutrophils","volume":"377","author":"Wang","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wen, S.H., Hong, Z.W., Chen, C.C., Chang, H.W., and Fu, H.W. (2021). Helicobacter pylori neutrophil-activating protein directly interacts with and activates toll-like receptor 2 to induce the secretion of interleukin-8 from neutrophils and ATRA-induced differentiated HL-60 cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111560"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1172\/JCI27177","article-title":"The neutrophil-activating protein of Helicobacter pylori promotes Th1 immune responses","volume":"116","author":"Amedei","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/1521-4141(200203)32:3<671::AID-IMMU671>3.0.CO;2-5","article-title":"The neutrophil-activating protein (HP-NAP) of Helicobacter pylori is a potent stimulant of mast cells","volume":"32","author":"Montemurro","year":"2002","journal-title":"Eur. J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1080\/21505594.2015.1043505","article-title":"Helicobacter pylori neutrophil-activating protein induces release of histamine and interleukin-6 through G protein-mediated MAPKs and PI3K\/Akt pathways in HMC-1 cells","volume":"6","author":"Tsai","year":"2015","journal-title":"Virulence"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1086\/319280","article-title":"Helicobacter pylori neutrophil-activating protein stimulates tissue factor and plasminogen activator inhibitor-2 production by human blood mononuclear cells","volume":"183","author":"Montemurro","year":"2001","journal-title":"J. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.4049\/jimmunol.1400339","article-title":"Vector-encoded Helicobacter pylori neutrophil-activating protein promotes maturation of dendritic cells with Th1 polarization and improved migration","volume":"193","author":"Ramachandran","year":"2014","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"962","DOI":"10.4049\/jimmunol.158.2.962","article-title":"T helper 1 effector cells specific for Helicobacter pylori in the gastric antrum of patients with peptic ulcer disease","volume":"158","author":"Manghetti","year":"1997","journal-title":"J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/S0016-5085(98)70531-1","article-title":"Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype","volume":"114","author":"Bamford","year":"1998","journal-title":"Gastroenterology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1128\/IAI.66.2.444-447.1998","article-title":"Neutrophil-activating protein mediates adhesion of Helicobacter pylori to sulfated carbohydrates on high-molecular-weight salivary mucin","volume":"66","author":"Namavar","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1128\/JB.186.4.949-955.2004","article-title":"Proteomic analysis of the sarcosine-insoluble outer membrane fraction of Helicobacter pylori strain 26695","volume":"186","author":"Baik","year":"2004","journal-title":"J. Bacteriol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1574-695X.2001.tb01567.x","article-title":"Flow cytometric analysis of the localization of Helicobacter pylori antigens during different growth phases","volume":"30","author":"Blom","year":"2001","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1002\/prca.200800192","article-title":"Proteomic and functional characterization of the outer membrane vesicles from the gastric pathogen Helicobacter pylori","volume":"3","author":"Mullaney","year":"2009","journal-title":"Proteomics. Clin. Appl."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.3389\/fimmu.2018.01466","article-title":"Helicobacter pylori outer membrane vesicle size determines their mechanisms of host cell entry and protein content","volume":"9","author":"Turner","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1523-5378.2009.00678.x","article-title":"The C-terminal region of HPNAP activates neutrophils and promotes their adhesion to endothelial cells","volume":"14","author":"Kottakis","year":"2009","journal-title":"Helicobacter"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/MEG.0b013e32831c50c9","article-title":"Effects of mastic gum Pistacia lentiscus var. Chia on innate cellular immune effectors","volume":"21","author":"Kottakis","year":"2009","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.molmed.2020.05.006","article-title":"TLR2 as a therapeutic target in bacterial infection","volume":"26","author":"Simpson","year":"2020","journal-title":"Trends Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Hu, W., and Spaink, H.P. (2022). The role of TLR2 in infectious diseases caused by mycobacteria: From cell biology to therapeutic target. Biology, 11.","DOI":"10.3390\/biology11020246"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1002\/med.21553","article-title":"Recent clinical trends in Toll-like receptor targeting therapeutics","volume":"39","author":"Anwar","year":"2019","journal-title":"Med. Res. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/s41573-020-0078-4","article-title":"Soluble ligands as drug targets","volume":"19","author":"Attwood","year":"2020","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41467-021-27655-0","article-title":"Helical structure motifs made searchable for functional peptide design","volume":"13","author":"Tsai","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nrgastro.2017.57","article-title":"Helicobacter pylori infection and antibiotic resistance: A WHO high priority?","volume":"14","author":"Dang","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S1473-3099(17)30753-3","article-title":"Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis","volume":"18","author":"Tacconelli","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/S1286-4579(03)00124-2","article-title":"Molecular and cellular mechanisms of action of the vacuolating cytotoxin (VacA) and neutrophil-activating protein (HP-NAP) virulence factors of Helicobacter pylori","volume":"5","author":"Montecucco","year":"2003","journal-title":"Microbes. Infect."},{"key":"ref_52","first-page":"337","article-title":"Helicobacter pylori and gastric epithelial cells: From gastritis to cancer","volume":"24","author":"Penta","year":"2005","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12964-017-0171-4","article-title":"From inflammation to gastric cancer\u2014The importance of Hedgehog\/GLI signaling in Helicobacter pylori-induced chronic inflammatory and neoplastic diseases","volume":"15","author":"Wessler","year":"2017","journal-title":"Cell Commun. Signal."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.3748\/wjg.15.2381","article-title":"Detection and evaluation of antibodies against neutrophil-activating protein of Helicobacter pylori in patients with gastric cancer","volume":"15","author":"Long","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2942","DOI":"10.1002\/ijc.28621","article-title":"A CagA-independent cluster of antigens related to the risk of noncardia gastric cancer: Associations between Helicobacter pylori antibodies and gastric adenocarcinoma explored by multiplex serology","volume":"134","author":"Song","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"944139","DOI":"10.3389\/fimmu.2022.944139","article-title":"HP-NAP of Helicobacter pylori: The power of the immunomodulation","volume":"13","author":"Codolo","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1046\/j.1365-2567.2003.01711.x","article-title":"Enhanced mucosal and systemic immune responses to Helicobacter pylori antigens through mucosal priming followed by systemic boosting immunizations","volume":"110","author":"Vajdy","year":"2003","journal-title":"Immunology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3252","DOI":"10.1128\/IAI.72.6.3252-3259.2004","article-title":"Therapeutic vaccination against Helicobacter pylori in the beagle dog experimental model: Safety, immunogenicity, and efficacy","volume":"72","author":"Rossi","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1053\/j.gastro.2008.05.054","article-title":"Safety and immunogenicity of an intramuscular Helicobacter pylori vaccine in noninfected volunteers: A phase I study","volume":"135","author":"Malfertheiner","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/S2468-1253(18)30125-0","article-title":"Efficacy, immunogenicity, and safety of a parenteral vaccine against Helicobacter pylori in healthy volunteers challenged with a Cag-positive strain: A randomised, placebo-controlled phase 1\/2 study","volume":"3","author":"Malfertheiner","year":"2018","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"349","DOI":"10.3389\/fcimb.2017.00349","article-title":"Oral immunization with a multivalent epitope-based vaccine, based on NAP, urease, HSP60, and HpaA, provides therapeutic effect on H. pylori Infection in Mongolian gerbils","volume":"7","author":"Guo","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.3389\/fimmu.2019.01185","article-title":"Therapeutic protection against H. pylori infection in Mongolian gerbils by oral immunization with a tetravalent epitope-based vaccine with polysaccharide adjuvant","volume":"10","author":"Guo","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1016\/j.vaccine.2020.02.036","article-title":"Oral immunization of mice with a multivalent therapeutic subunit vaccine protects against Helicobacter pylori infection","volume":"38","author":"Liu","year":"2020","journal-title":"Vaccine"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1080\/21645515.2020.1744364","article-title":"Parenteral immunization with a cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) adjuvanted Helicobacter pylori vaccine induces protective immunity against H. pylori infection in mice","volume":"16","author":"Chen","year":"2020","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6435","DOI":"10.1038\/s41598-018-24879-x","article-title":"Production and delivery of Helicobacter pylori NapA in Lactococcus lactis and its protective efficacy and immune modulatory activity","volume":"8","author":"Peng","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.omto.2021.04.016","article-title":"Concurrent expression of HP-NAP enhances antitumor efficacy of oncolytic vaccinia virus but not for Semliki Forest virus","volume":"21","author":"Ma","year":"2021","journal-title":"Mol. Ther. Oncolytics."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1111\/j.1462-5822.2008.01217.x","article-title":"The neutrophil-activating protein of Helicobacter pylori down-modulates Th2 inflammation in ovalbumin-induced allergic asthma","volume":"10","author":"Codolo","year":"2008","journal-title":"Cell. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"fnw288","DOI":"10.1093\/femsle\/fnw288","article-title":"Systemic and mucosal pre-administration of recombinant Helicobacter pylori neutrophil-activating protein prevents ovalbumin-induced allergic asthma in mice","volume":"364","author":"Zhou","year":"2017","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5819","DOI":"10.1007\/s00253-017-8370-x","article-title":"The recombinant fusion protein of cholera toxin B and neutrophil-activating protein expressed on Bacillus subtilis spore surface suppresses allergic inflammation in mice","volume":"101","author":"Dong","year":"2017","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1007\/s10753-016-0375-6","article-title":"A recombinant DNA plasmid encoding the sIL-4R-NAP fusion protein suppress airway inflammation in an OVA-induced mouse model of asthma","volume":"39","author":"Liu","year":"2016","journal-title":"Inflammation"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1080\/08923973.2020.1806869","article-title":"HP-NAP ameliorates OXA-induced atopic dermatitis symptoms in mice","volume":"42","author":"Guo","year":"2020","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1111\/cea.13489","article-title":"Oral administration of recombinant Bacillus subtilis spores expressing Helicobacter pylori neutrophil-activating protein suppresses peanut allergy via up-regulation of Tregs","volume":"49","author":"Mai","year":"2019","journal-title":"Clin. Exp. Allergy"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00262-011-1087-2","article-title":"HP-NAP inhibits the growth of bladder cancer in mice by activating a cytotoxic Th1 response","volume":"61","author":"Codolo","year":"2012","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.intimp.2015.08.027","article-title":"Antitumor and immunomodulatory effects of recombinant fusion protein rMBP-NAP through TLR-2 dependent mechanism in tumor bearing mice","volume":"29","author":"Wang","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1139\/cjpp-2017-0186","article-title":"Recombinant protein rMBP-NAP restricts tumor progression by triggering antitumor immunity in mouse metastatic lung cancer","volume":"96","author":"Wang","year":"2018","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Codolo, G., Facchinello, N., Papa, N., Bertocco, A., Coletta, S., Benna, C., Dall\u2019Olmo, L., Mocellin, S., Tiso, N., and de Bernard, M. (2022). Macrophage-mediated melanoma reduction after HP-NAP treatment in a zebrafish xenograft model. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031644"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ejpb.2020.08.013","article-title":"Nanoparticle-based immunotherapy of breast cancer using recombinant Helicobacter pylori proteins","volume":"155","author":"Soleimani","year":"2020","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1038\/mt.2012.4","article-title":"Expression of immunomodulatory neutrophil-activating protein of Helicobacter pylori enhances the antitumor activity of oncolytic measles virus","volume":"20","author":"Iankov","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1038\/mt.2013.153","article-title":"An infection-enhanced oncolytic adenovirus secreting H. pylori neutrophil-activating protein with therapeutic effects on neuroendocrine tumors","volume":"21","author":"Ramachandran","year":"2013","journal-title":"Mol. Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e141614","DOI":"10.1172\/JCI141614","article-title":"Immunostimulatory bacterial antigen-armed oncolytic measles virotherapy significantly increases the potency of anti-PD1 checkpoint therapy","volume":"131","author":"Panagioti","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1038\/s41551-022-00875-5","article-title":"CAR T cells expressing a bacterial virulence factor trigger potent bystander antitumour responses in solid cancers","volume":"6","author":"Jin","year":"2022","journal-title":"Nat. Biomed. Eng."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1080\/1040841X.2017.1291578","article-title":"The study of H. pylori putative candidate factors for single- and multi-component vaccine development","volume":"43","author":"Mirzaei","year":"2017","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4795","DOI":"10.1016\/j.vaccine.2013.07.085","article-title":"Measles virus expressed Helicobacter pylori neutrophil-activating protein significantly enhances the immunogenicity of poor immunogens","volume":"31","author":"Iankov","year":"2013","journal-title":"Vaccine"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"493","DOI":"10.3389\/fmicb.2015.00493","article-title":"Helicobacter pylori neutrophil-activating protein: A potential Treg modulator suppressing allergic asthma?","volume":"6","author":"Sehrawat","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_85","first-page":"4707","article-title":"Toll-like receptor agonist rMBP-NAP enhances antitumor cytokines production and CTL activity of peripheral blood mononuclear cells from patients with lung cancer","volume":"16","author":"Ding","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.jconrel.2009.10.032","article-title":"Nanosystem drug targeting: Facing up to complex realities","volume":"141","author":"Ruenraroengsak","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_87","first-page":"14","article-title":"TLR agonist rHP-NAP as an adjuvant of dendritic cell-based vaccine to enhance anti-melanoma response","volume":"17","author":"Hou","year":"2020","journal-title":"Iran. J. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/91\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:45:22Z","timestamp":1760147122000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/91"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,21]]},"references-count":87,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24010091"],"URL":"https:\/\/doi.org\/10.3390\/ijms24010091","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,21]]}}}