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Trends in Microbiology Nov 2021Antimicrobial resistance is an increasing global threat and alternative treatments substituting failing antibiotics are urgently needed. Vaccines are recognized as... (Review)
Review
Antimicrobial resistance is an increasing global threat and alternative treatments substituting failing antibiotics are urgently needed. Vaccines are recognized as highly effective tools to mitigate antimicrobial resistance; however, the selection of bacterial antigens as vaccine candidates remains challenging. In recent years, advances in mass spectrometry-based proteomics have led to the development of so-called immunopeptidomics approaches that allow the untargeted discovery of bacterial epitopes that are presented on the surface of infected cells. Especially for intracellular bacterial pathogens, immunopeptidomics holds great promise to uncover antigens that can be encoded in viral vector- or nucleic acid-based vaccines. This review provides an overview of immunopeptidomics studies on intracellular bacterial pathogens and considers future directions and challenges in advancing towards next-generation vaccines.
Topics: Antigens, Bacterial; Bacterial Vaccines; Mass Spectrometry; Proteomics; Vaccine Development
PubMed: 34030969
DOI: 10.1016/j.tim.2021.04.010 -
Immunology Letters May 2018Live bacteria, including attenuated bacteria and probiotics, can be engineered to deliver target antigen to excite the host immune system. The preponderance of these... (Review)
Review
Live bacteria, including attenuated bacteria and probiotics, can be engineered to deliver target antigen to excite the host immune system. The preponderance of these live bacterial vaccine vectors is that they can stimulate durable humoral and cellular immunity. Moreover, delivery strategies of heterologous antigen in live bacterial promote the applications of new vaccine development. Genetic technologies are evolving, which potentiate the developing of heterologous antigen delivery systems, including bacterial surface display system, bacterial secretion system and balanced lethal vector system. Although the live bacterial vaccine vector is a powerful adjuvant, certain disadvantages, such as safety risk, must also be taken into account. In this review, we compare the development of representative live bacterial vectors, and summarize the main characterizations of the various delivery strategies of heterologous antigen in live vector vaccines.
Topics: Animals; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Infections; Bacterial Vaccines; Genetic Vectors; Humans; Immunity, Cellular; Immunity, Heterologous; Immunity, Humoral
PubMed: 29550258
DOI: 10.1016/j.imlet.2018.03.006 -
Cells Nov 2022The global threat of antimicrobial resistance (AMR) poses a difficult challenge, as underscored by the World Health Organization (WHO), which identifies AMR as one of...
The global threat of antimicrobial resistance (AMR) poses a difficult challenge, as underscored by the World Health Organization (WHO), which identifies AMR as one of the three greatest threats to human health [...].
Topics: Humans; Drug Resistance, Bacterial; Bacterial Vaccines; Anti-Bacterial Agents; World Health Organization
PubMed: 36497063
DOI: 10.3390/cells11233803 -
Frontiers in Immunology 2018The ongoing, and very serious, threat from antimicrobial resistance necessitates the development and use of preventative measures, predominantly vaccination.... (Review)
Review
The ongoing, and very serious, threat from antimicrobial resistance necessitates the development and use of preventative measures, predominantly vaccination. Polysaccharide-based vaccines have provided a degree of success in limiting morbidity from disseminated bacterial infections, including those caused by the major human obligate pathogens, , and . Limitations of these polysaccharide vaccines, such as partial coverage and induced escape leading to persistence of disease, provide a compelling argument for the development of protein vaccines. In this review, we briefly chronicle approaches that have yielded licensed vaccines before highlighting reverse vaccinology 2.0 and its potential application in the discovery of novel bacterial protein vaccine candidates. Technical challenges and research gaps are also discussed.
Topics: Animals; Bacterial Infections; Bacterial Vaccines; Humans; Vaccinology
PubMed: 30349542
DOI: 10.3389/fimmu.2018.02315 -
Allergy and Asthma Proceedings Nov 2022Orally or sublingually administered lysates of mixed respiratory pathogenic bacteria have been used in Europe, Asia, and other parts of the world, but not the United... (Review)
Review
Orally or sublingually administered lysates of mixed respiratory pathogenic bacteria have been used in Europe, Asia, and other parts of the world, but not the United States, since the mid 1950s, first to prevent recurrent respiratory tract infections, later to prevent wheezing and asthma exacerbations associated with respiratory infections, and, more recently, for the treatment of allergic rhinitis. The apparent success of this treatment contrasts with the negative experience of treating with injections of similar mixed respiratory bacterial vaccines (MRBV or BV) to prevent asthma exacerbations associated with respiratory infections that was once common practice but abandoned ∼50 years ago. Textbooks and articles on the use of injected BVs to prevent asthma exacerbations associated with respiratory infections were reviewed, including a number of, randomized, double-blind, placebo controlled (RDBPC) studies the results of which were predominantly negative that contributed to the abandonment of this treatment. Also reviewed were more recent articles from Europe and China, which report both clinical and immunologic support for the use of the orally and sublingually administered mixed respiratory bacterial lysates (MRBL or BL). A review of five RDBPC studies of the parenteral use of BVs for prevention of asthma exacerbations conducted by leading international allergists in the 1950s and 1960s showed, in a combined 532 patients, an overall reduction of asthma attacks by 4.9% over placebo. However, in five studies in 1126 patients of oral or sublingual treatment with BLs, the reduction in respiratory infections, wheezing episodes, and asthma exacerbations was 42.6% over placebo. Reported results with oral and sublingual BLs are far superior to the historical performance of injected BVs. Possible reasons for this difference are discussed, but none is clearly responsible for the difference in clinical results.
Topics: Humans; Respiratory Sounds; Asthma; Rhinitis, Allergic; Respiratory Tract Infections; Bacterial Vaccines; Randomized Controlled Trials as Topic
PubMed: 36335411
DOI: 10.2500/aap.2022.43.220053 -
Brazilian Journal of Microbiology :... 2014Genetically attenuated microorganisms, pathogens, and some commensal bacteria can be engineered to deliver recombinant heterologous antigens to stimulate the host immune... (Review)
Review
Genetically attenuated microorganisms, pathogens, and some commensal bacteria can be engineered to deliver recombinant heterologous antigens to stimulate the host immune system, while still offering good levels of safety. A key feature of these live vectors is their capacity to stimulate mucosal as well as humoral and/or cellular systemic immunity. This enables the use of different forms of vaccination to prevent pathogen colonization of mucosal tissues, the front door for many infectious agents. Furthermore, delivery of DNA vaccines and immune system stimulatory molecules, such as cytokines, can be achieved using these special carriers, whose adjuvant properties and, sometimes, invasive capacities enhance the immune response. More recently, the unique features and versatility of these vectors have also been exploited to develop anti-cancer vaccines, where tumor-associated antigens, cytokines, and DNA or RNA molecules are delivered. Different strategies and genetic tools are constantly being developed, increasing the antigenic potential of agents delivered by these systems, opening fresh perspectives for the deployment of vehicles for new purposes. Here we summarize the main characteristics of the different types of live bacterial vectors and discuss new applications of these delivery systems in the field of vaccinology.
Topics: Animals; Bacterial Infections; Bacterial Vaccines; Drug Carriers; Humans; Neoplasms; Organisms, Genetically Modified; Vaccines, Attenuated
PubMed: 25763014
DOI: 10.1590/s1517-83822014000400001 -
Pathogens and Disease Jul 2018Gut infections triggered by pathogenic bacteria lead to most frequently occurring diarrhea in humans accounting for million deaths annually. Currently, only a few... (Review)
Review
Gut infections triggered by pathogenic bacteria lead to most frequently occurring diarrhea in humans accounting for million deaths annually. Currently, only a few licensed vaccines are available against these pathogens for mostly travelers moving to diarrheal endemic areas. Besides commercialized vaccines, there are many formulations that are either under clinical or pre-clinical stages of development and despite several efforts to improve safety, immunogenicity and efficacy, none of them can confer long-term protective immunity, for which repeated booster doses are always recommended. Further in many countries, financial, social and political constraints have jeopardized vaccine development program against these pathogens that enforce us to gather knowledge on safety, tolerability, immunogenicity and protective efficacy regarding the same. In this review, we analyze safety and efficacy issues of vaccines against five major gut bacteria causing enteric infections. The article also simultaneously describes several barriers for vaccine development and further discusses possible strategies to enhance immunogenicity and efficacy.
Topics: Bacterial Vaccines; Cholera; Drug Development; Enterobacteriaceae Infections; Humans
PubMed: 30052916
DOI: 10.1093/femspd/fty057 -
Trends in Biotechnology Aug 2019Design of a reliable process for bacterial antigen production requires understanding of and control over critical process parameters. Current methods for process design... (Review)
Review
Design of a reliable process for bacterial antigen production requires understanding of and control over critical process parameters. Current methods for process design use extensive screening experiments for determining ranges of critical process parameters yet fail to give clear insights into how they influence antigen potency. To address this gap, we propose to apply constraint-based, genome-scale metabolic models to reduce the need of experimental screening for strain selection and to optimize strains based on model driven iterative Design-Build-Test-Learn (DBTL) cycles. Application of these systematic methods has not only increased the understanding of how metabolic network properties influence antigen potency, but also allows identification of novel critical process parameters that need to be controlled to achieve high process reliability.
Topics: Antigens, Bacterial; Bacterial Vaccines; Bioengineering; Humans; Technology, Pharmaceutical; Vaccine Potency
PubMed: 30961926
DOI: 10.1016/j.tibtech.2019.03.005 -
Journal of Controlled Release :... Dec 2002The application of new strategies to develop effective vaccines is essential in modern veterinary medicine. The bacterial ghost system is a novel vaccine delivery system... (Review)
Review
The application of new strategies to develop effective vaccines is essential in modern veterinary medicine. The bacterial ghost system is a novel vaccine delivery system endowed with intrinsic adjuvant properties. Bacterial ghosts are nonliving Gram-negative bacterial cell envelopes devoid of cytoplasmic contents while maintaining their cellular morphology and native surface antigenic structures including bioadhesive properties. They are produced by PhiX174 protein E-mediated lysis of Gram-negative bacteria. The intrinsic adjuvant properties of bacterial ghost preparations enhance immune responses against envelope bound antigens, including T-cell activation and mucosal immunity. Since native and foreign antigens can be expressed in the envelope complex of ghosts before E-mediated lysis, multiple antigens of various origins can be presented to the immune system simultaneously. The advantages of bacterial ghosts include the simplicity of the production method, safety, independence from the cold chain, and versatility as a combination vaccine.
Topics: Animals; Bacterial Vaccines; Drug Delivery Systems; Gram-Negative Bacteria; Humans; Veterinary Drugs
PubMed: 12480307
DOI: 10.1016/s0168-3659(02)00267-5 -
Frontiers in Immunology 2019Reverse Vaccinology (RV) is a widely used approach to identify potential vaccine candidates (PVCs) by screening the proteome of a pathogen through computational... (Review)
Review
Reverse Vaccinology (RV) is a widely used approach to identify potential vaccine candidates (PVCs) by screening the proteome of a pathogen through computational analyses. Since its first application in Group B (MenB) vaccine in early 1990's, several software programs have been developed implementing different flavors of the first RV protocol. However, there has been no comprehensive review to date on these different RV tools. We have compared six of these applications designed for bacterial vaccines (NERVE, Vaxign, VaxiJen, Jenner-predict, Bowman-Heinson, and VacSol) against a set of 11 pathogens for which a curated list of known bacterial protective antigens (BPAs) was available. We present results on: (1) the comparison of criteria and programs used for the selection of PVCs (2) computational runtime and (3) performances in terms of fraction of proteome identified as PVC, fraction and enrichment of BPA identified in the set of PVCs. This review demonstrates that none of the programs was able to recall 100% of the tested set of BPAs and that the output lists of proteins are in poor agreement suggesting in the process of prioritize vaccine candidates not to rely on a single RV tool response. Singularly the best balance in terms of fraction of a proteome predicted as good candidate and recall of BPAs has been observed by the machine-learning approach proposed by Bowman (1) and enhanced by Heinson (2). Even though more performing than the other approaches it shows the disadvantage of limited accessibility to non-experts users and strong dependence between results and training dataset composition. In conclusion we believe that to significantly enhance the performances of next RV methods further studies should focus on the enhancement of accuracy of the existing protein annotation tools and should leverage on the assets of machine-learning techniques applied to biological datasets expanded also through the incorporation and curation of bacterial proteins characterized by negative experimental results.
Topics: Animals; Antigens, Bacterial; Bacterial Infections; Bacterial Vaccines; Computational Biology; Datasets as Topic; High-Throughput Screening Assays; Humans; Machine Learning; Proteomics; Software; Vaccinology
PubMed: 30837982
DOI: 10.3389/fimmu.2019.00113