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

Malfertheiner, Peter; Selgrad, Michael; Wex, Thomas; Romi, Benedetta; Borgogni, Erica; Spensieri, Fabiana; Zedda, Luisanna; Ruggiero, Paolo; Pancotto, Laura; Censini, Stefano; Palla, Emanuela; Kanesa-thasan, Niranjan; Scharschmidt, Bruce F.; Rappuoli, Rino; Graham, David Y.; Schiavetti, Francesca; Giudice, Giuseppe Del

doi:10.1016/s2468-1253(18)30125-0

Cited by 78 publications

(56 citation statements)

References 41 publications

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“…38). 45 Despite this disappointing finding, the study did provide indisputable evidence for the spontaneous clearance of H pylori infection in 9 of 15 participants in the placebo group. 45 Despite this disappointing finding, the study did provide indisputable evidence for the spontaneous clearance of H pylori infection in 9 of 15 participants in the placebo group.…”

Section: Clinical Trials Of H Pylori Vaccine Candidatesmentioning

confidence: 90%

“…Indeed, the H pylori antigens CagA and VacA induced some protective immunity against H pylori infection in mice 47 and were well tolerated by and elicited strong memory responses in H pylori-negative volunteers, 44 yet when tested as a subunit vaccine with NapA in a phase 1/2 clinical trial, were unable to confer protection in volunteers challenged with a CagA-positive H pylori strain. 45 Despite this disappointing finding, the study did provide indisputable evidence for the spontaneous clearance of H pylori infection in 9 of 15 participants in the placebo group. 45 This observation is interesting and suggests the existence of some form of natural immunity against H pylori infection in otherwise naïve hosts, warranting further investigation.…”

Section: Clinical Trials Of H Pylori Vaccine Candidatesmentioning

confidence: 90%

“…42 To overcome the harsh effects of the gastrointestinal tract on the immunogenicity of vaccine preparations, Liu et al 43 developed an approach based on the use of HP55/poly(n-butylcyanoacrylate) (PBCA) NPs to carry an H pylori subunit vaccine (CCF) for oral administration. 44,45 Peng et al 46 43 Oral vaccination of mice with HP55/PBCA-CCF NPs promoted the production of serum antigen-specific antibodies and secretory IgA, as well as pro-inflammatory cytokine production by splenic lymphocytes.…”

Section: Optimization Of the Delivery System For An Helicobacter Pymentioning

confidence: 99%

“…43 H pylori NapA is a candidate vaccine antigen that has been tested in clinical trials. 44,45 Peng et al 46…”

Section: Optimization Of the Delivery System For An Helicobacter Pymentioning

confidence: 99%

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Review: Helicobacter: Inflammation, immunology, and vaccines

Lehours

Ferrero

2019

Helicobacter

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Chronic inflammation induced by Helicobacter pylori infection is a critical factor in the development of peptic ulcer disease and gastric cancer. Central to this inflammation is the initiation of pro‐inflammatory signaling cascades within epithelial cells, in particular those mediated by two sensors of bacterial cell wall components, nucleotide‐binding oligomerization domain‐containing protein 1 (NOD1) and alpha‐protein kinase 1 (ALPK1). H pylori is, however, also highly adept at mitigating inflammation in the host, thereby restricting tissue damage and favoring bacterial persistence. H pylori modulates host immune responses by altering cytokine signaling in epithelial and myeloid cells, which results in increased proliferation of regulatory T cells and downregulation of effector T‐cell responses. H pylori vacuolating cytotoxin A (VacA) has been shown to play an important role in the dampening of immune responses and induction of immune tolerance capable of protecting against asthma. It is also possible to generate protective immune responses by immunization with various H pylori antigens or their epitopes, in combination with an adjuvant, though this for now has only been shown in mouse models. Novel non‐toxic adjuvants, consisting of modified bacterial enterotoxins or nanoparticles, have recently been developed that may not only enhance vaccine efficacy, but also help translate candidate vaccines to the clinic. This review will summarize the main discoveries in the past year regarding host immune responses to H pylori infection, as well as the design of new vaccine approaches against this infection.

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Section: Clinical Trials Of H Pylori Vaccine Candidatesmentioning

confidence: 90%

Section: Clinical Trials Of H Pylori Vaccine Candidatesmentioning

confidence: 90%

Section: Optimization Of the Delivery System For An Helicobacter Pymentioning

confidence: 99%

“…43 H pylori NapA is a candidate vaccine antigen that has been tested in clinical trials. 44,45 Peng et al 46…”

Section: Optimization Of the Delivery System For An Helicobacter Pymentioning

confidence: 99%

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Review: Helicobacter: Inflammation, immunology, and vaccines

Lehours

Ferrero

2019

Helicobacter

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“…Data from another study testing an intramuscular vaccine in young healthy adult volunteers did not show adequate protection against the infection in this group. But interestingly, an enhanced immune reaction was seen in participants who received the vaccine (compared to placebo) [125]. All study participants were challenged with inoculation of a CagA positive H. pylori strain and it was interesting that the adult immune system proved to be quite competent to repel this infection with more than half of the subjects in the placebo arm failed to establish the infection.…”

Section: H Pylori Eradicationmentioning

confidence: 99%

The Rationale and Efficacy of Primary and Secondary Prevention in Adenocarcinomas of the Upper Gastrointestinal Tract

Bornschein

Bird‐Lieberman

Malfertheiner

2019

Dig Dis

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While the primary risk factor for oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett’s oesophagus (BO) is gastro-oesophageal reflux, the infection with Helicobacter pylori (H. pylori) is the dominant risk factor for gastric cancer. Reduction of reflux by dietary measures and proton pump inhibitors has some merits in OAC prevention, and the chemopreventive effect of Aspirin and statins is being widely investigated; however, improved outcome in OAC occurs primarily as the result of secondary prevention. Early detection of neoplastic lesions in Barrett’s metaplasia can be achieved by surveillance endoscopies. Novel endoscopic imaging modalities carry similar importance as the endoscopic treatment techniques as without detection of early lesions, therapy cannot be applied. Minimally invasive approaches are currently being investigated to identify patients with BO who are at particular risk of neoplastic progression. While dietary factors also play an important role in the prevention of gastric cancer and chemoprevention seems to be promising, the most beneficial effect has been shown for the eradication of H. pylori infection, which results in at least a one third reduction of gastric cancer risk. This effect can be further improved if the eradication takes place prior to the development of pre-neoplastic gastric conditions such as mucosal atrophy or intestinal metaplasia (IM). The definition of the “point of no return”, after which eradication is less effective, is of high importance, although H. pylori eradication can still be beneficial even at more advance stages of mucosal changes. For this reason, patients with advanced atrophy and IM should undergo endoscopic surveillance in the same way as patients with BO. There is also need for development of non-invasive tests to identify patients at high risk of progression to gastric cancer to improve outcome of these surveillance approaches.

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Potential antigen candidates for subunit vaccine development against Helicobacter pylori infection

Eslami

Yousefi

Ghasemian

et al. 2019

Journal Cellular Physiology

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Helicobacter pylori (H. pylori) is a resident bacterium in the stomach that accounts for 75% cases of gastric cancer. In this review, we comprehensively studied published papers on H. pylori vaccines using Google Scholar and NCBI databases to gather information about vaccines against H. pylori. Considering the pivotal roles of the enzyme urease (in production of NH 3 and neutralization of the acidic medium of the stomach), cytotoxinassociated gene A, and vacuolating cytotoxin A proteins in H. pylori infection, they could be the best candidates for the construction of recombinant vaccines. The outer membrane porins (Hop), blood group antigen-binding adhesin (BabA), sialic acid-binding adhesin (SabA), and outer inflammatory protein A, play significant roles in binding of bacterium to human gastric tissues, and because binding is the first step in bacterial fixation and colonization, these antigens also can be considered as suitable candidates for designing vaccines. Likely, other significant bacterial antigens, such as NapA (chemotactic factor for recruitment of human neutrophils and monocytes to the site of infection), duodenal ulcer promoting protein A (to promote duodenal ulcer), and Hsp60 (as a molecular chaperon for activation of urease enzyme), can be used in the construction of subunit vaccines. New vaccines in use currently, such as DNA vaccines and subunit vaccines, can efficiently replace the dead and attenuated vaccines. Nonetheless, the results show that urease enzyme is most used compared with bacterial components in the designing and construction of recombinant vaccines. The BabA and SabA antigens belong to the outer membrane porins family in H. pylori and are required for binding and fixation of the bacterium to the human gastric tissues. K E Y W O R D SCagA, Helicobacter pylori, recombinant vaccine, urease, VacA

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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

Cited by 78 publications

References 41 publications

Review: Helicobacter: Inflammation, immunology, and vaccines

Review: Helicobacter: Inflammation, immunology, and vaccines

The Rationale and Efficacy of Primary and Secondary Prevention in Adenocarcinomas of the Upper Gastrointestinal Tract

Potential antigen candidates for subunit vaccine development against Helicobacter pylori infection

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