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The Lancet. Microbe Feb 2023Vaccines can be highly effective tools in combating antimicrobial resistance as they reduce infections caused by antibiotic-resistant bacteria and antibiotic consumption... (Review)
Review
Vaccines can be highly effective tools in combating antimicrobial resistance as they reduce infections caused by antibiotic-resistant bacteria and antibiotic consumption associated with disease. This Review looks at vaccine candidates that are in development against pathogens on the 2017 WHO bacterial priority pathogen list, in addition to Clostridioides difficile and Mycobacterium tuberculosis. There were 94 active preclinical vaccine candidates and 61 active development vaccine candidates. We classified the included pathogens into the following four groups: Group A consists of pathogens for which vaccines already exist-ie, Salmonella enterica serotype Typhi, Streptococcus pneumoniae, Haemophilus influenzae type b, and M tuberculosis. Group B consists of pathogens with vaccines in advanced clinical development-ie, extra-intestinal pathogenic Escherichia coli, Salmonella enterica serotype Paratyphi A, Neisseria gonorrhoeae, and C difficile. Group C consists of pathogens with vaccines in early phases of clinical development-ie, enterotoxigenic E coli, Klebsiella pneumoniae, non-typhoidal Salmonella, Shigella spp, and Campylobacter spp. Finally, group D includes pathogens with either no candidates in clinical development or low development feasibility-ie, Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, Helicobacter pylori, Enterococcus faecium, and Enterobacter spp. Vaccines are already important tools in reducing antimicrobial resistance and future development will provide further opportunities to optimise the use of vaccines against resistance.
Topics: Anti-Bacterial Agents; Bacterial Vaccines; Escherichia coli; Drug Resistance, Bacterial; Enterococcus faecium
PubMed: 36528040
DOI: 10.1016/S2666-5247(22)00303-2 -
Nature Communications Oct 2022Listeria monocytogenes is a foodborne intracellular bacterial pathogen leading to human listeriosis. Despite a high mortality rate and increasing antibiotic resistance...
Listeria monocytogenes is a foodborne intracellular bacterial pathogen leading to human listeriosis. Despite a high mortality rate and increasing antibiotic resistance no clinically approved vaccine against Listeria is available. Attenuated Listeria strains offer protection and are tested as antitumor vaccine vectors, but would benefit from a better knowledge on immunodominant vector antigens. To identify novel antigens, we screen for Listeria peptides presented on the surface of infected human cell lines by mass spectrometry-based immunopeptidomics. In between more than 15,000 human self-peptides, we detect 68 Listeria immunopeptides from 42 different bacterial proteins, including several known antigens. Peptides presented on different cell lines are often derived from the same bacterial surface proteins, classifying these antigens as potential vaccine candidates. Encoding these highly presented antigens in lipid nanoparticle mRNA vaccine formulations results in specific CD8 T-cell responses and induces protection in vaccination challenge experiments in mice. Our results can serve as a starting point for the development of a clinical mRNA vaccine against Listeria and aid to improve attenuated Listeria vaccines and vectors, demonstrating the power of immunopeptidomics for next-generation bacterial vaccine development.
Topics: Animals; Bacterial Proteins; Bacterial Vaccines; CD8-Positive T-Lymphocytes; Humans; Immunodominant Epitopes; Liposomes; Listeria; Listeria monocytogenes; Listeriosis; Membrane Proteins; Mice; Nanoparticles; Vaccines, Attenuated; Vaccines, Synthetic; mRNA Vaccines
PubMed: 36241641
DOI: 10.1038/s41467-022-33721-y -
Cell Reports Jan 2022MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology....
MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology. However, its mechanism of action remains poorly understood. Here, we find that intranasal prophylaxis with MV130 modulates the lung immune landscape and provides long-term heterologous protection against viral respiratory infections in mice. Intranasal administration of MV130 provides protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection. Moreover, pharmacological inhibition of trained immunity with metformin abrogates the protection conferred by MV130 against influenza A virus respiratory infection. MV130 induces reprogramming of both mouse bone marrow progenitor cells and in vitro human monocytes, promoting an enhanced cytokine production that relies on a metabolic shift. Our results unveil that the mucosal administration of a fully inactivated bacterial vaccine provides protection against viral infections by a mechanism associated with the induction of trained immunity.
Topics: Administration, Intranasal; Animals; Antibodies, Viral; Bacteria; Bacterial Vaccines; Candidiasis; Cell Line; Chlorocebus aethiops; Cytokines; Humans; Immunity, Mucosal; Influenza A virus; L Cells; Lung; Metformin; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocytes; Orthomyxoviridae Infections; Respiratory Mucosa; Respiratory Tract Infections; Vaccines, Inactivated
PubMed: 34986349
DOI: 10.1016/j.celrep.2021.110184 -
Toxins Sep 2017Botulinum neurotoxins (BoNT) cause the flaccid paralysis of botulism by inhibiting the release of acetylcholine from motor neurons. There are seven serotypes of BoNT... (Review)
Review
Botulinum neurotoxins (BoNT) cause the flaccid paralysis of botulism by inhibiting the release of acetylcholine from motor neurons. There are seven serotypes of BoNT (A-G), with limited therapies, and no FDA approved vaccine for botulism. An investigational formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was used to vaccinate people who are at high risk of contracting botulism. However, this formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was losing potency and was discontinued. This article reviews the different vaccines being developed to replace the discontinued toxoid vaccine. These vaccines include DNA-based, viral vector-based, and recombinant protein-based vaccines. DNA-based vaccines include plasmids or viral vectors containing the gene encoding one of the BoNT heavy chain receptor binding domains (HC). Viral vectors reviewed are adenovirus, influenza virus, rabies virus, Semliki Forest virus, and Venezuelan Equine Encephalitis virus. Among the potential recombinant protein vaccines reviewed are HC, light chain-heavy chain translocation domain, and chemically or genetically inactivated holotoxin.
Topics: Animals; Bacterial Vaccines; Botulism; Humans
PubMed: 28869493
DOI: 10.3390/toxins9090268 -
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 -
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 -
Expert Review of Vaccines Jan 2017Syphilis, caused by the spirochete Treponema pallidum subspecies pallidum, continues to be a globally prevalent disease despite remaining susceptible to penicillin... (Review)
Review
Syphilis, caused by the spirochete Treponema pallidum subspecies pallidum, continues to be a globally prevalent disease despite remaining susceptible to penicillin treatment. Syphilis vaccine development is a viable preventative approach that will serve to complement public health-oriented syphilis prevention, screening and treatment initiatives to deliver a two-pronged approach to stemming disease spread worldwide. Areas covered: This article provides an overview of the need for development of a syphilis vaccine, summarizes significant information that has been garnered from prior syphilis vaccine studies, discusses the critical aspects of infection that would have to be targeted by a syphilis vaccine, and presents the current understanding within the field of the correlates of protection needed to be achieved through vaccination. Expert commentary: Syphilis vaccine development should be considered a priority by industry, regulatory and funding agencies, and should be appropriately promoted and supported.
Topics: Animals; Bacterial Vaccines; Disease Models, Animal; Disease Transmission, Infectious; Drug Discovery; Humans; Syphilis; Treponema pallidum
PubMed: 27328030
DOI: 10.1080/14760584.2016.1203262 -
MSphere 2018Lactic acid bacteria (LAB) have been utilized since the 1990s for therapeutic heterologous gene expression. The ability of LAB to elicit an immune response against... (Review)
Review
Lactic acid bacteria (LAB) have been utilized since the 1990s for therapeutic heterologous gene expression. The ability of LAB to elicit an immune response against expressed foreign antigens has led to their exploration as potential mucosal vaccine candidates. LAB vaccine vectors offer many attractive advantages: simple, noninvasive administration (usually oral or intranasal), the acceptance and stability of genetic modifications, relatively low cost, and the highest level of safety possible. Experimentation using LAB of the genus has become popular in recent years due to their ability to elicit strong systemic and mucosal immune responses. This article reviews vaccine constructs, including species, antigen expression, model organisms, and immune responses, with a primary focus on viral and bacterial antigens.
Topics: Administration, Intranasal; Administration, Oral; Antigens, Bacterial; Antigens, Viral; Bacterial Vaccines; Drug Carriers; Humans; Lactobacillus; Vaccines, Synthetic
PubMed: 29769376
DOI: 10.1128/mSphere.00061-18 -
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 -
Gut Microbes Nov 2020Enteric viral and bacterial infections continue to be a leading cause of mortality and morbidity in young children in low-income and middle-income countries, the... (Review)
Review
Enteric viral and bacterial infections continue to be a leading cause of mortality and morbidity in young children in low-income and middle-income countries, the elderly, and immunocompromised individuals. Vaccines are considered an effective and practical preventive approach against the predominantly fecal-to-oral transmitted gastroenteritis particularly in the resource-limited countries or regions where implementation of sanitation systems and supply of safe drinking water are not quickly achievable. While vaccines are available for a few enteric pathogens including rotavirus and cholera, there are no vaccines licensed for many other enteric viral and bacterial pathogens. Challenges in enteric vaccine development include immunological heterogeneity among pathogen strains or isolates, a lack of animal challenge models to evaluate vaccine candidacy, undefined host immune correlates to protection, and a low protective efficacy among young children in endemic regions. In this article, we briefly updated the progress and challenges in vaccines and vaccine development for the leading enteric viral and bacterial pathogens including rotavirus, human calicivirus, , enterotoxigenic (ETEC), cholera, nontyphoidal , and , and introduced a novel epitope- and structure-based vaccinology platform known as MEFA (multiepitope fusion antigen) and the application of MEFA for developing broadly protective multivalent vaccines against heterogenous pathogens.
Topics: Animals; Bacterial Vaccines; Drug Development; Gastroenteritis; Humans; Viral Vaccines
PubMed: 32552414
DOI: 10.1080/19490976.2020.1770666