Development of vaccines against Helicobacter pylori

被引:64
作者
Del Giudice, Giuseppe [1 ]
Malfertheiner, Peter [2 ]
Rappuoli, Rino [1 ]
机构
[1] Novartis Vaccines & Diagnost, Res Ctr, I-53100 Siena, Italy
[2] Otto Von Guericke Univ, Klin Gastroenterol Hepatol & Infektiol, D-39120 Magdeburg, Germany
关键词
adjuvant; antibody response; cellular response; Helicobacter pylori; pathogenesis; recombinant protein; vaccine; vaccine delivery; NEUTROPHIL-ACTIVATING PROTEIN; REGULATORY T-CELLS; COLI ENTEROTOXIN ADJUVANT; GASTRIC-CANCER PATIENTS; B-CELL; VACUOLATING CYTOTOXIN; PROTECTIVE IMMUNITY; ORAL IMMUNIZATION; INDUCED REDUCTION; ADOPTIVE TRANSFER;
D O I
10.1586/ERV.09.62
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
Helicobacter pylori is a Gram-negative, microaerophilic bacterium adapted to survive in the stomach of humans where it can cause peptide ulcers and gastric cancer. Although effective antibiotic treatment exists, there is a consensus that vaccines are necessary to limit the severity of this infection. Great progress has been made since its discovery 25 years ago in understanding the virulence factors and several aspects of the pathogenesis of the H. pylori gastric diseases. Several key bacterial factors have been identified: urease, vacuolating cytotoxin, cytotoxin-associated antigen, the pathogenicity island, neutrophil-activating protein, and among others. These proteins, in their native or recombinant forms, have been shown to confer protection against infectious challenge with H. pylori in experimental animal models. It is not known, however, through which effector mechanisms this protection is achieved. Nevertheless, a number of clinical trials in healthy volunteers have been conducted using urease given orally as a soluble protein or expressed in bacterial vectors with limited results. Recently, a mixture of H. pylori antigens was reported to be highly immunogenic in H. pylori-negative volunteers following intramuscular administration of the vaccine with aluminium hydroxide as an adjuvant. These data show that vaccination against this pathogen is feasible. More research is required to understand the immunological mechanisms underlying immune-mediate protection.
引用
收藏
页码:1037 / 1049
页数:13
相关论文
共 124 条
[1]
Correlation of T cell response and bacterial clearance in human volunteers challenged with Helicobacter pylori revealed by randomised controlled vaccination with Ty21a-based Salmonella vaccines [J].
Aebischer, T. ;
Bumann, D. ;
Epple, H. J. ;
Metzger, W. ;
Schneider, T. ;
Cherepnev, G. ;
Walduck, A. K. ;
Kunkel, D. ;
Moos, V. ;
Loddenkemper, C. ;
Jiadze, I. ;
Panasyuk, M. ;
Stolte, M. ;
Graham, D. Y. ;
Zeitz, M. ;
Meyer, T. F. .
GUT, 2008, 57 (08) :1065-1072
[2]
IgA antibodies impair resistance against Helicobacter pylori infection:: Studies on immune evasion in IL-10-deficient mice [J].
Akhiani, AA ;
Stensson, A ;
Schön, K ;
Lycke, NY .
JOURNAL OF IMMUNOLOGY, 2005, 174 (12) :8144-8153
[3]
Vaccine-induced immunity against Helicobacter pylori infection is impaired in IL-18-deficient mice [J].
Akhiani, AA ;
Schön, K ;
Lycke, N .
JOURNAL OF IMMUNOLOGY, 2004, 173 (05) :3348-3356
[4]
Protection against Helicobacter pylori infection following immunization is IL-12-dependent and mediated by Th1 cells [J].
Akhiani, AA ;
Pappo, J ;
Kabok, Z ;
Schön, K ;
Gao, W ;
Franzén, LE ;
Lycke, N .
JOURNAL OF IMMUNOLOGY, 2002, 169 (12) :6977-6984
[5]
The neutrophil-activating protein of Helicobacter pylori promotes Th1 immune responses [J].
Amedei, A ;
Cappon, A ;
Codolo, G ;
Cabrelle, A ;
Polenghi, A ;
Benagiano, M ;
Tasca, E ;
Azzurri, A ;
D'Elios, MM ;
Del Prete, G ;
de Bernard, M .
JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (04) :1092-1101
[6]
Host-bacterial interactions in Helicobacter pylori infection [J].
Amieva, Manuel R. ;
El-Omar, Emad M. .
GASTROENTEROLOGY, 2008, 134 (01) :306-323
[7]
Pilot study of phoP/phoQ-deleted Salmonella enterica serovar Typhimurium expressing Helicobacter pylori urease in adult volunteers [J].
Angelakopoulos, H ;
Hohmann, EL .
INFECTION AND IMMUNITY, 2000, 68 (04) :2135-2141
[8]
Role of type IV secretion in Helicobacter pylori pathogenesis [J].
Backert, Steffen ;
Selbach, Matthias .
CELLULAR MICROBIOLOGY, 2008, 10 (08) :1573-1581
[9]
Helicobacter pylori CagA induces a transition from polarized to invasive phenotypes in MDCK cells [J].
Bagnoli, F ;
Buti, L ;
Tompkins, L ;
Covacci, A ;
Amieva, MR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (45) :16339-16344
[10]
Safety and efficacy of low dose Escherichia coli enterotoxin adjuvant for urease based oral immunisation against Helicobacter pylori in healthy volunteers [J].
Banerjee, S ;
Medina-Fatimi, A ;
Nichols, R ;
Tendler, D ;
Michetti, M ;
Simon, J ;
Kelly, CP ;
Monath, TP ;
Michetti, P .
GUT, 2002, 51 (05) :634-640