One of the most prevalent human infections is Helicobacter pylori (H. pylori), which affects more than half of the global population. Although H. pylori infections are widespread, only a minority of individuals develop severe gastroduodenal disorders. The global resistance of H. pylori to antibiotics has reached concerning levels, significantly impacting the effectiveness of treatment. Consequently, the development of vaccines targeting virulence factors may present a viable alternative for the treatment and prevention of H. pylori infections. This review aims to provide a comprehensive overview of the current understanding of H. pylori infection, with a particular focus on its virulence factors, pathophysiology, and vaccination strategies. This review discusses various virulence factors associated with H. pylori, such as cytotoxin-associated gene A (cagA), vacuolating cytotoxin gene (vacA), outer membrane proteins (OMPs), neutrophil-activated protein (NAP), urease (ure), and catalase. The development of vaccines based on these virulence characteristics is essential for controlling infection and ensuring long-lasting protection. Various vaccination strategies and formulations have been tested in animal models; however, their effectiveness and reproducibility in humans remain uncertain. Different types of vaccines, including vector-based vaccines, inactivated whole cells, genetically modified protein-based subunits, and multiepitope nucleic acid (DNA) vaccines, have been explored. While some vaccines have demonstrated promising results in murine models, only a limited number have been successfully tested in humans. This article provides a thorough evaluation of recent research on H. pylori virulence genes and vaccination methods, offering valuable insights for future strategies to address this global health challenge.

Helicobacter pylori (H. pylori) is a Gram-negative, spiral-shaped bacterium that colonizes the gastric epithelium and is associated with a range of gastrointestinal disorders, exhibiting a global prevalence of approximately 50%. Despite the availability of treatment options, H. pylori frequently reemerges and demonstrates increasing antibiotic resistance, which diminishes the efficacy of conventional therapies. Consequently, it is imperative to explore non-antibiotic treatment alternatives to mitigate the inappropriate use of antibiotics. This review examines H. pylori infection, encompassing transmission pathways, treatment modalities, antibiotic resistance, and eradication strategies. Additionally, it discusses alternative therapeutic approaches such as probiotics, anti-biofilm agents, phytotherapy, phototherapy, phage therapy, lactoferrin therapy, and vaccine development. These strategies aim to reduce antimicrobial resistance and enhance treatment outcomes for H. pylori infections. While alternative therapies can maintain low bacterial levels, they do not achieve complete eradication of H. pylori. These therapies are designed to bolster the immune response, minimize side effects, and provide gastroprotective benefits, rendering them suitable for adjunctive use alongside conventional treatments. Probiotics may serve as adjunctive therapy for H. pylori; however, their effectiveness as a monotherapy is limited. Photodynamic and phage therapies exhibit potential in targeting H. pylori infections, including those caused by drug-resistant strains, without the use of antibiotics. The development of a reliable vaccine is also critical for the eradication of H. pylori. This review identifies candidate antigens such as VacA, CagA, and HspA, along with various vaccine formulations, including vector-based and subunit vaccines. Some vaccines have demonstrated efficacy in clinical trials, while others have shown robust immune protection in preclinical studies. Nevertheless, each of the aforementioned alternative therapies requires thorough preclinical and clinical evaluation to ascertain their efficacy, side effects, cost-effectiveness, and patient compliance.

Advancements in vaccine technology are increasingly focused on leveraging the unique properties of both pathogenic and commensal bacteria. This revolutionary approach harnesses the diverse immune modulatory mechanisms and bacterial biology inherent in different bacterial species enhancing vaccine efficacy and safety. Pathogenic bacteria, known for their ability to induce robust immune responses, are being studied for their potential to be engineered into safe, attenuated vectors that can target specific diseases with high precision. Concurrently, commensal bacteria, which coexist harmlessly with their hosts and contribute to immune system regulation, are also being explored as novel delivery systems and in microbiome-based therapy. These bacteria can modulate immune responses, offering a promising avenue for developing effective and personalized vaccines. Integrating the distinctive characteristics of pathogenic and commensal bacteria with advanced bacterial engineering techniques paves the way for innovative vaccine and therapeutic platforms that could address a wide range of infectious diseases and potentially non-infectious conditions. This holistic approach signifies a paradigm shift in vaccine development and immunotherapy, emphasizing the intricate interplay between the bacteria and the immune systems to achieve optimal immunological outcomes.

Helicobacter pylori infection causes chronic gastritis, ulcers, and gastric cancer, making it a threat to human health. Despite the use of antibiotic therapy, the global prevalence of H. pylori infection remains high, necessitating early eradication measures. Immunotherapy, especially vaccine development, is a promising solution in this direction, albeit the selection of an appropriate animal model is critical in efficient vaccine production. Accordingly, we conducted a literature, search and summarized the commonly used H. pylori strains, H. pylori infection-related animal models, and models for evaluating H. pylori vaccines. Based on factors such as the ability to replicate human diseases, strain compatibility, vaccine types, and eliciting of immune responses, we systematically compared the advantages and disadvantages of different animal models, to obtain the informed recommendations. In addition, we have proposed novel perspectives on H. pylori-related animal models to advance research and vaccine evaluation for the prevention and treatment of diseases such as gastric cancer.

Background: H. pylori (Helicobacter pylori) infections typically occur in early childhood. Although the prevalence of H. pylori in children is lower than that in adults, the eradication rate of this infection in children is relatively low because of resistance. In this study, we analyzed personalized treatment strategies to achieve treatment goals based on H. pylori resistance characteristics. This retrospective single-center study was conducted between January 2019 and December 2022 and enrolled 1,587 children who presented with upper gastrointestinal symptoms and underwent endoscopy. H. pylori culturing and antimicrobial susceptibility testing were performed. Results: Culture-positive results for H. pylori were obtained in 535 children. The resistance rates to clarithromycin (CLA), metronidazole (MET), and levofloxacin (LEV) were 39.8%, 78.1%, and 20.2%, respectively. None of the isolates were resistant to tetracycline (TET), amoxicillin (AMO), or furazolidone (FZD). Double resistance rates to CLA + MET, CLA + LEV, and MET + LEV were 19.1%, 3.0%, and 5.8%, respectively. Notably, triple-resistant to CLA + MET + LEV was 9.7%. Based on susceptibility tests, individualized triple therapy [proton pump inhibitor (PPI) +AMO + CLA/MET] was selected for 380 children with H. pylori sensitive to MET and/or CLA. In 155 children resistant to CLA and MET, bismuth-based quadruple therapy was recommended; for unable to receive bismuth, concomitant therapy was recommended for 14 children (<8 years of age); triple therapy with TET was recommended for 141 children (>8 years of age), with 43 children (>14 years of age) requiring FZD rather than TET. Conclusion: Resistance to H. pylori in Chinese children was relatively poor. Personalized therapy regimens should be based on susceptibility tests and avoided factors associated with treatment failure.

Helicobacter pylori (H. pylori) colonizes the stomach epithelium of half the world's population and is responsible for various digestive diseases and even stomach cancer. Vaccine-mediated protection against H. pylori infection depends primarily on the specific mucosal and T-cell responses. In this study, the synthetic lipopeptide vaccines, Hp4 (Pam2 Cys modified UreB T-cell epitope) and Hp10 (Pam2 Cys modified CagA T/B cell combined epitope), not only induce the bone marrow derived dendritic cells (BMDCs) maturation by activating a variety of pattern-recognition receptors (PRRs) such as Toll-like receptor (TLR), Nod-like receptor (NLR), and retinoic acid-inducing gene (RIG) I-like receptor (RLR), and but also stimulate BMDCs to secret cytokines that have the potential to modulate T-cell activation and differentiation. Although intranasal immunization with Hp4 or Hp10 elicits robust epitope-specific T-cell responses in mice, only Hp10 confers protection against H. pylori infection, possibly due to the fact that Hp10 also induces substantial specific sIgA response at mucosal sites. Interestingly, Hp4 elevates the protective response against H. pylori infection of Hp10 when administrated in combination, characterized by better protective effect and enhanced specific T-cell and mucosal antibody responses. The results suggest that synthetic lipopeptide vaccines based on the epitopes derived from the protective antigens are promising candidates for protection against H. pylori infection.

Helicobacter pylori infection often occurs in early childhood, and can last a lifetime if not treated with medication. H. pylori infection can also cause a variety of stomach diseases, which can only be treated with a combination of antibiotics. Combinations of antibiotics can cure H. pylori infection, but it is easy to relapse and develop drug resistance. Therefore, a vaccine is a promising strategy for prevention and therapy for the infection of H. pylori. After decades of research and development, there has been no appearance of any H. pylori vaccine reaching the market, unfortunately. This review summarizes the aspects of candidate antigens, immunoadjuvants, and delivery systems in the long journey of H. pylori vaccine research, and also introduces some clinical trials that have displayed encouraging or depressing results. Possible reasons for the inability of an H. pylori vaccine to be available over the counter are cautiously discussed and some propositions for the future of H. pylori vaccines are outlined.

Alternative therapies and vaccination are essential to combat the emergence of multidrug-resistant Helicobacter pylori and to prevent the development of gastroduodenal diseases. This review aimed to systematically review recent studies on alternative therapies, i.e., probiotics, nanoparticles, and natural products from plants, as well as recent progress in H. pylori vaccines at the preclinical stage. Articles published from January 2018 to August 2022 were systematically searched using PubMed, Scopus, Web of Science, and Medline. After the screening process, 45 articles were eligible for inclusion in this review. Probiotics (n = 9 studies) and natural products from plants (n = 28 studies) were observed to inhibit the growth of H. pylori, improve immune response, reduce inflammation, and reduce the pathogenic effects of H. pylori virulence factors. Natural products from plants also showed anti-biofilm activity against H. pylori. However, clinical trials of natural products from plants and probiotics are still lacking. A paucity of data assessing the nanoparticle activity of N-acylhomoserine lactonase-stabilized silver against H. pylori was observed. Nonetheless, one nanoparticle study showed anti-biofilm activity against H. pylori. Promising results of H. pylori vaccine candidates (n = 7) were observed at preclinical stage, including elicitation of a humoral and mucosal immune response. Furthermore, the application of new vaccine technology including multi-epitope and vector-based vaccines using bacteria was investigated at the preclinical stage. Taken together, probiotics, natural products from plants, and nanoparticles exhibited antibacterial activity against H. pylori. New vaccine technology shows promising results against H. pylori.

Helicobacter pylori (H. pylori) infection, which affects approximately half of the world's population, remains a serious public health problem. As H. pylori infection leads to a number of gastric pathologies, including inflammation, gastroduodenal ulcers, and malignancies, early detection and treatment are crucial to preventing the spread of the infection. Multiple extragastric complications, such as iron deficiency anaemia, immune thrombocytopenic purpura, vitamin B12 deficiency, diabetes mellitus, cardiovascular diseases, and certain neurological disorders, have also been linked to H. pylori infection. An awareness of H. pylori and associated health hazards is necessary to minimize or even eradicate the infection. Therefore, there is an urgent need to raise the standards for the currently employed diagnostic, eradication, alternative treatment strategies. In addition, a brief overview of traditional and cutting-edge approaches that have proven effective in identifying and managing H. pylori is needed. Based on the test and laboratory equipment available and patient clinical characteristics, the optimal diagnostic approach requires weighing several factors. The pathophysiology and pathogenic mechanisms of H. pylori should also be studied, focusing more on the infection-causing virulence factors of this bacterium. Accordingly, this review aims to demonstrate the various diagnostic, pathophysiological, therapeutic, and eradication tactics available for H. pylori, emphasizing both their advantages and disadvantages. Invasive methods (such as quick urease testing, biopsy, or culture) or noninvasive methods (such as breath tests, stool investigations, or serological tests) can be used. We also present the most recent worldwide recommendations along with scientific evidence for treating H. pylori. In addition to the current antibiotic regimens, alternative therapies may also be considered. It is imperative to eradicate the infections caused by H. pylori as soon as possible to prevent problems and the development of stomach cancer. In conclusion, significant advances have been made in identifying and treating H. pylori. To improve eradication rates, peptide mass fingerprinting can be used as a diagnostic tool, and vaccines can also eliminate the infection.

Helicobacter pylori (H. pylori) infection is the main factor leading to some gastric diseases. Currently, H. pylori infection is primarily treated with antibiotics. However, with the widespread application of antibiotics, H. pylori resistance to antibiotics has also gradually increased year by year. Vaccines may be an alternative solution to clear H. pylori.

By reviewing the recent progress on H. pylori vaccines, we expected it to lead to more research efforts to accelerate breakthroughs in this field.

We searched the research on H. pylori vaccine in recent years through PubMed®, and then classified and summarized these studies.

The study of the pathogenic mechanism of H. pylori has led to the development of vaccines using some antigens, such as urease, catalase, and heat shock protein (Hsp). Based on these antigens, whole-cell, subunit, nucleic acid, vector, and H. pylori exosome vaccines have been tested.

At present, researchers have developed many types of vaccines, such as whole cell vaccines, subunit vaccines, vector vaccines, etc. However, although some of these vaccines induced protective immunity in mouse models, only a few were able to move into human trials. We propose that mRNA vaccine may play an important role in preventing or treating H. pylori infection. The current study shows that we have developed various types of vaccines based on the virulence factors of H. pylori. However, only a few vaccines have entered human clinical trials. In order to improve the efficacy of vaccines, it is necessary to enhance T-cell immunity.

We should fully understand the pathogenic mechanism of H. pylori and find its core antigen as a vaccine target.

Helicobacter pylori (H. pylori) infection is chronic and etiologically linked to gastric cancer (GC) derived from gastric epithelium. The potential mechanism is complex, covering chronic inflammation, epithelial senescence, NF-κB activation, the cytotoxin-associated gene A protein translocation, and related abnormal signaling pathways. In clinical practice, the test-and-treat strategy, endoscopy-based strategy, and (family-based) screen-and-treat strategy are recommended to detect H. pylori and prevent GC. It has been demonstrated that the decreasing annual incidence of GC is largely attributable to the management of H. pylori. This study reviews the current clinical practice of H. pylori on the detection and eradication, alternative treatment strategies, and related problems and advances, and hopes to contribute to the better clinical management of H. pylori.