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World Journal of Gastroenterology Mar 2016Over three decades have passed since the discovery of Helicobacter pylori (H. pylori), and yet many questions about its treatment remain unanswered. For example, there... (Review)
Review
Over three decades have passed since the discovery of Helicobacter pylori (H. pylori), and yet many questions about its treatment remain unanswered. For example, there is no certainty regarding continued use of current antibiotic therapy against H. pylori. The bad news is that even combined regimens are also unable to eradicate bacterial colonization. The worst problem with H. pylori chemotherapy is that even if we identify the most successful regimen, it cannot eliminate the risk of re-infection. This problem is further complicated by the fact that clinicians have no information as to whether probiotics are useful or not. Moreover, to date, we have no large scale produced vaccine effective against H. pylori. Due to the relatively rapid and abundant dissemination of guidelines globally reported concerning management of gastric cancer prevention and therapeutic regimens, clinicians may choose a vaccine as better effective weapon against H. pylori. Therefore, a radical shift in adopted strategies is needed to guide ultimate decisions regarding H. pylori management. In light of failures in vaccine projects, we should identify better vaccine design targeting conserved/essential genes. The unique character and persistence of H. pylori pose obstacles to making an effective vaccine. Preferably, in developing countries, the best reasonable and logical approach is to recommend prophylactic H. pylori vaccine among children as an obligatory national program to limit primary colonization. Trying to produce a therapeutic vaccine would be postponed until later. In reality, we should not forget to prescribe narrow spectrum antibiotics. In the current review, I draw a route to define the best adopted strategy against this rogue bacterium.
Topics: Animals; Anti-Bacterial Agents; Bacterial Vaccines; Drug Resistance, Bacterial; Helicobacter Infections; Helicobacter pylori; Humans; Probiotics; Remission Induction; Treatment Outcome
PubMed: 27003991
DOI: 10.3748/wjg.v22.i11.3150 -
Molecules (Basel, Switzerland) Jul 2018During the last decade there has been a growing interest in glycoimmunology, a relatively new research field dealing with the specific interactions of carbohydrates with... (Review)
Review
During the last decade there has been a growing interest in glycoimmunology, a relatively new research field dealing with the specific interactions of carbohydrates with the immune system. Pathogens' cell surfaces are covered by a thick layer of oligo- and polysaccharides that are crucial virulence factors, as they mediate receptors binding on host cells for initial adhesion and organism invasion. Since in most cases these saccharide structures are uniquely exposed on the pathogen surface, they represent attractive targets for vaccine design. Polysaccharides isolated from cell walls of microorganisms and chemically conjugated to immunogenic proteins have been used as antigens for vaccine development for a range of infectious diseases. However, several challenges are associated with carbohydrate antigens purified from natural sources, such as their difficult characterization and heterogeneous composition. Consequently, glycoconjugates with chemically well-defined structures, that are able to confer highly reproducible biological properties and a better safety profile, are at the forefront of vaccine development. Following on from our previous review on the subject, in the present account we specifically focus on the most recent advances in the synthesis and preliminary immunological evaluation of next generation glycoconjugate vaccines designed to target bacterial and fungal infections that have been reported in the literature since 2011.
Topics: Animals; Bacterial Infections; Bacterial Vaccines; Fungal Vaccines; Glycoconjugates; Humans; Mycoses; Virulence Factors
PubMed: 30011851
DOI: 10.3390/molecules23071712 -
Emerging Infectious Diseases Jun 2015Several candidates for a vaccine against Burkholderia pseudomallei, the causal bacterium of melioidosis, have been developed, and a rational approach is now needed to...
Several candidates for a vaccine against Burkholderia pseudomallei, the causal bacterium of melioidosis, have been developed, and a rational approach is now needed to select and advance candidates for testing in relevant nonhuman primate models and in human clinical trials. Development of such a vaccine was the topic of a meeting in the United Kingdom in March 2014 attended by international candidate vaccine developers, researchers, and government health officials. The focus of the meeting was advancement of vaccines for prevention of natural infection, rather than for protection from the organism's known potential for use as a biological weapon. A direct comparison of candidate vaccines in well-characterized mouse models was proposed. Knowledge gaps requiring further research were identified. Recommendations were made to accelerate the development of an effective vaccine against melioidosis.
Topics: Animals; Bacterial Vaccines; Burkholderia pseudomallei; Capital Financing; Disease Models, Animal; Humans; Melioidosis; Mice
PubMed: 25992835
DOI: 10.3201/eid2106.141480 -
Human Vaccines & Immunotherapeutics 2014Clostridium difficile infection (CDI) is recognized as a major cause of nosocomial diseases ranging from antibiotic related diarrhea to fulminant colitis. Emergence... (Review)
Review
Clostridium difficile infection (CDI) is recognized as a major cause of nosocomial diseases ranging from antibiotic related diarrhea to fulminant colitis. Emergence during the last 2 decades of C. difficile strains associated with high incidence, severity and lethal outcomes has increased the challenges for CDI treatment. A limited number of drugs have proven to be effective against CDI and concerns about antibiotic resistance as well as recurring disease solicited the search for novel therapeutic strategies. Active vaccination provides the attractive opportunity to prevent CDI, and intense research in recent years led to development of experimental vaccines, 3 of which are currently under clinical evaluation. This review summarizes recent achievements and remaining challenges in the field of C. difficile vaccines, and discusses future perspectives in view of newly-identified candidate antigens.
Topics: Anti-Bacterial Agents; Bacterial Vaccines; Clinical Trials as Topic; Clostridioides difficile; Clostridium Infections; Cross Infection; Diarrhea; Drug Discovery; Humans
PubMed: 24637887
DOI: 10.4161/hv.28428 -
Current Opinion in Infectious Diseases Feb 2011The aim is to review recent findings on immunity and vaccine development to Chlamydia trachomatis. (Review)
Review
PURPOSE OF REVIEW
The aim is to review recent findings on immunity and vaccine development to Chlamydia trachomatis.
RECENT FINDINGS
There is increasing knowledge on the interactions between C. trachomatis and infected host cells. During genital infection the organism avoids generating protective immunity but immune responses to a number of chlamydial proteins have been associated with reproductive tract pathology. Various vaccine and adjuvant preparations have been tried experimentally. Information generated by proteomics and complex studies of serological and T-lymphocyte immune responses points to novel vaccine candidates.
SUMMARY
C. trachomatis, an obligate intracellular bacterium, is the commonest sexually transmitted infection worldwide and is associated with reproductive pathology. To develop rational vaccines it is necessary to understand the complex lifecycle of the organism, the host immune response to infection and how these relate to disease. Infection does not prevent re-infection and antibiotic treatment prevents antibody production at a population level. It remains unclear what type of immune response would be sufficient to prevent infection and/or re-infection. Although the prevalence and demographics of infection and the severity of disease associations suggest that it would be desirable, there is no vaccine currently available. A number of studies have identified novel vaccine candidates.
Topics: Adjuvants, Immunologic; Bacterial Vaccines; Chlamydia trachomatis; Host-Pathogen Interactions; Humans; Lymphogranuloma Venereum
PubMed: 21124214
DOI: 10.1097/QCO.0b013e3283421081 -
Expert Review of Vaccines Jul 2009Tularemia, caused by the Gram-negative bacterium Francisella tularensis, can be contracted by the bite of an arthropod vector or by inhalation. This disease occurs... (Review)
Review
Tularemia, caused by the Gram-negative bacterium Francisella tularensis, can be contracted by the bite of an arthropod vector or by inhalation. This disease occurs relatively infrequently but can be severe and even life-threatening if untreated. Until recently, there were few laboratories studying this organism; however, concerns over its potential use as a biological weapon have led to renewed attention to F. tularensis research, particularly in the area of vaccine development. Advances in the ability to genetically manipulate F. tularensis, along with knowledge gained from the creation and refinement of attenuated bacterial vaccines for other diseases, continue to foster significant progress in the development of live-attenuated bacterial vaccines, as well as defined antigen and subunit vaccines.
Topics: Bacterial Vaccines; Drug Design; Francisella tularensis; Humans; Tularemia; Vaccines, Attenuated
PubMed: 19538114
DOI: 10.1586/erv.09.51 -
Frontiers in Cellular and Infection... 2018is the causative agent of tularemia and a Tier I bioterrorism agent. In the 1900s, several vaccines were developed against tularemia including the killed "Foshay"... (Review)
Review
is the causative agent of tularemia and a Tier I bioterrorism agent. In the 1900s, several vaccines were developed against tularemia including the killed "Foshay" vaccine, subunit vaccines comprising protein(s) or lipoproteins(s) in an adjuvant formulation, and the Live Vaccine Strain (LVS); none were licensed in the U.S.A. or European Union. The LVS vaccine retains toxicity in humans and animals-especially mice-but has demonstrated efficacy in humans, and thus serves as the current gold standard for vaccine efficacy studies. The U.S.A. 2001 anthrax bioterrorism attack spawned renewed interest in vaccines against potential biowarfare agents including . Since live attenuated-but not killed or subunit-vaccines have shown promising efficacy and since vaccine efficacy against respiratory challenge with less virulent subspecies or , or against non-respiratory challenge with virulent subsp. (Type A) does not reliably predict vaccine efficacy against respiratory challenge with virulent subsp. , the route of transmission and species of greatest concern in a bioterrorist attack, in this review, we focus on live attenuated tularemia vaccine candidates tested against respiratory challenge with virulent Type A strains, including homologous vaccines derived from mutants of subsp. , and subsp. , and heterologous vaccines developed using viral or bacterial vectors to express immunoprotective antigens. We compare the virulence and efficacy of these vaccine candidates with that of LVS and discuss factors that can significantly impact the development and evaluation of live attenuated tularemia vaccines. Several vaccines meet what we would consider the minimum criteria for vaccines to go forward into clinical development-safety greater than LVS and efficacy at least as great as LVS, and of these, several meet the higher standard of having efficacy ≥LVS in the demanding mouse model of tularemia. These latter include LVS with deletions in , or ; LVS Δ that also overexpresses Type VI Secretion System (T6SS) proteins; FSC200 with a deletion in ; the single deletional mutant of SCHU S4, and a heterologous prime-boost vaccine comprising LVS Δ and expressing T6SS proteins.
Topics: Animals; Bacterial Capsules; Bacterial Proteins; Bacterial Vaccines; Bioterrorism; Disease Models, Animal; Francisella tularensis; Heat-Shock Proteins; Humans; Lipoproteins; Listeria monocytogenes; Mice; Oxidative Stress; Sequence Deletion; Superoxide Dismutase; Tularemia; Type VI Secretion Systems; Vaccines, Attenuated; Vaccines, Subunit; Virulence
PubMed: 29868510
DOI: 10.3389/fcimb.2018.00154 -
The Lancet. Infectious Diseases Mar 2006Bacterial pneumonia is a substantial cause of childhood morbidity and mortality worldwide, but determination of pathogen-specific burden remains a challenge. In less... (Review)
Review
Bacterial pneumonia is a substantial cause of childhood morbidity and mortality worldwide, but determination of pathogen-specific burden remains a challenge. In less developed settings, the WHO recommended guidelines are useful for initiating care, but are non-specific. Blood culture has low sensitivity, while radiological findings are non-specific and do not discriminate between viral and bacterial causes of pneumonia. In vaccine probe studies, efficacy is dependent on the specificity of the study outcome to detect pneumonia and the impact of the vaccine on the selected outcome, and may underestimate the true burden of bacterial pneumonia. The rising incidence of antibiotic resistance, emerging respiratory pathogens, potential replacement pneumococcal disease following widespread introduction of pneumococcal polysaccharide-protein conjugate vaccine, the limited specificity of chest radiography, and the poor sensitivity of blood culture are substantial obstacles to accurate surveillance. We provide an overview of the diagnostic challenges of bacterial pneumonia and highlight the need for refining the current diagnostic approach to ensure adequate epidemiological surveillance of childhood pneumonia and the success, or otherwise, of any immunisation strategies.
Topics: Bacterial Vaccines; Blood; Child, Preschool; Drug Resistance, Bacterial; Humans; Immunization Programs; Infant; Infant, Newborn; Pneumococcal Vaccines; Pneumonia, Bacterial; Population Surveillance
PubMed: 16500596
DOI: 10.1016/S1473-3099(06)70411-X -
Virulence Jan 2014Gram-negative bacterial (GNB) infections are a leading cause of serious infections both in hospitals and the community. The mortality remains high despite potent... (Review)
Review
Gram-negative bacterial (GNB) infections are a leading cause of serious infections both in hospitals and the community. The mortality remains high despite potent antimicrobials and modern supportive care. In the last decade invasive GNB have become increasingly resistant to commonly used antibiotics, and attempts to intervene with novel biological therapies have been unsuccessful. Earlier studies with antibodies directed against a highly conserved core region in the GNB lipopolysaccharide (LPS, or endotoxin) suggested that this approach may have therapeutic benefit, and led to the development of a subunit vaccine that has progressed to phase 1 clinical testing. Since only a few serogroups of GNB cause bacteremia, O-specific vaccines had been developed, but these were not deployed because of the availability of other therapeutic options at the time. Given the likelihood that new antibiotics will not be soon available, the development of vaccines and antibodies directed against endotoxin, both O and core antigens, deserves a "second look".
Topics: Bacterial Vaccines; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Lipopolysaccharides; Sepsis; Vaccination
PubMed: 23974910
DOI: 10.4161/viru.25965 -
Toxins Sep 2019is a broad genus of anaerobic, spore-forming, rod-shaped, Gram-positive bacteria that can be found in different environments all around the world. The genus includes... (Review)
Review
is a broad genus of anaerobic, spore-forming, rod-shaped, Gram-positive bacteria that can be found in different environments all around the world. The genus includes human and animal pathogens that produce potent exotoxins that cause rapid and potentially fatal diseases responsible for countless human casualties and billion-dollar annual loss to the agricultural sector. Diseases include botulism, tetanus, enterotoxemia, gas gangrene, necrotic enteritis, pseudomembranous colitis, blackleg, and black disease, which are caused by pathogenic . Due to their ability to sporulate, they cannot be eradicated from the environment. As such, immunization with toxoid or bacterin-toxoid vaccines is the only protective method against infection. Toxins recovered from cultures are inactivated to form toxoids, which are then formulated into multivalent vaccines. This review discusses the toxins, diseases, and toxoid production processes of the most common pathogenic species, including , , , , , and
Topics: Animals; Bacterial Toxins; Bacterial Vaccines; Clostridium; Clostridium Infections; Humans
PubMed: 31514424
DOI: 10.3390/toxins11090525