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Frontiers in Immunology 2023Syphilis is a sexually or vertically (mother to fetus) transmitted disease caused by the infection of subspecie (TPA). The incidence of syphilis has increased over the... (Review)
Review
Syphilis is a sexually or vertically (mother to fetus) transmitted disease caused by the infection of subspecie (TPA). The incidence of syphilis has increased over the past years despite the fact that this bacterium is an obligate human pathogen, the infection route is well known, and the disease can be successfully treated with penicillin. As complementary measures to preventive campaigns and early treatment of infected individuals, development of a syphilis vaccine may be crucial for controlling disease spread and/or severity, particularly in countries where the effectiveness of the aforementioned measures is limited. In the last century, several vaccine prototypes have been tested in preclinical studies, mainly in rabbits. While none of them provided protection against infection, some prototypes prevented bacteria from disseminating to distal organs, attenuated lesion development, and accelerated their healing. In spite of these promising results, there is still some controversy regarding the identification of vaccine candidates and the characteristics of a syphilis-protective immune response. In this review, we describe what is known about TPA immune response, and the main mechanisms used by this pathogen to evade it. Moreover, we emphasize the importance of integrating this knowledge, in conjunction with the characterization of outer membrane proteins (OMPs), to expedite the development of a syphilis vaccine that can protect against TPA infection.
Topics: Animals; Humans; Rabbits; Syphilis; Treponema pallidum; Immunity; Bacterial Vaccines
PubMed: 37090699
DOI: 10.3389/fimmu.2023.1126170 -
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 -
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 -
Clinical Microbiology Reviews Jul 2015Streptococcus pneumoniae (the pneumococcus) is an important human pathogen. Its virulence is largely due to its polysaccharide capsule, which shields it from the host... (Review)
Review
Streptococcus pneumoniae (the pneumococcus) is an important human pathogen. Its virulence is largely due to its polysaccharide capsule, which shields it from the host immune system, and because of this, the capsule has been extensively studied. Studies of the capsule led to the identification of DNA as the genetic material, identification of many different capsular serotypes, and identification of the serotype-specific nature of protection by adaptive immunity. Recent studies have led to the determination of capsular polysaccharide structures for many serotypes using advanced analytical technologies, complete elucidation of genetic basis for the capsular types, and the development of highly effective pneumococcal conjugate vaccines. Conjugate vaccine use has altered the serotype distribution by either serotype replacement or switching, and this has increased the need to serotype pneumococci. Due to great advances in molecular technologies and our understanding of the pneumococcal genome, molecular approaches have become powerful tools to predict pneumococcal serotypes. In addition, more-precise and -efficient serotyping methods that directly detect polysaccharide structures are emerging. These improvements in our capabilities will greatly enhance future investigations of pneumococcal epidemiology and diseases and the biology of colonization and innate immunity to pneumococcal capsules.
Topics: Bacterial Capsules; Bacterial Vaccines; Genome, Bacterial; Immunity, Innate; Polysaccharides, Bacterial; Serogroup; Streptococcus pneumoniae
PubMed: 26085553
DOI: 10.1128/CMR.00024-15 -
FEMS Microbiology Reviews Jan 2020Invasive Staphylococcus aureus infections are a leading cause of morbidity and mortality in both hospital and community settings, especially with the widespread... (Review)
Review
Invasive Staphylococcus aureus infections are a leading cause of morbidity and mortality in both hospital and community settings, especially with the widespread emergence of virulent and multi-drug resistant methicillin-resistant S. aureus strains. There is an urgent and unmet clinical need for non-antibiotic immune-based approaches to treat these infections as the increasing antibiotic resistance is creating a serious threat to public health. However, all vaccination attempts aimed at preventing S. aureus invasive infections have failed in human trials, especially all vaccines aimed at generating high titers of opsonic antibodies against S. aureus surface antigens to facilitate antibody-mediated bacterial clearance. In this review, we summarize the data from humans regarding the immune responses that protect against invasive S. aureus infections as well as host genetic factors and bacterial evasion mechanisms, which are important to consider for the future development of effective and successful vaccines and immunotherapies against invasive S. aureus infections in humans. The evidence presented form the basis for a hypothesis that staphylococcal toxins (including superantigens and pore-forming toxins) are important virulence factors, and targeting the neutralization of these toxins are more likely to provide a therapeutic benefit in contrast to prior vaccine attempts to generate antibodies to facilitate opsonophagocytosis.
Topics: Bacterial Toxins; Bacterial Vaccines; Humans; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Staphylococcus aureus; Virulence Factors
PubMed: 31841134
DOI: 10.1093/femsre/fuz030 -
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 -
Clinical and Experimental Immunology May 2019In this two-part series of reviews, we have invited experts in their fields to contribute articles on the status of vaccine research and development for emerging...
In this two-part series of reviews, we have invited experts in their fields to contribute articles on the status of vaccine research and development for emerging pathogens. This topic has been brought into sharp focus in recent years following significant outbreaks of viral diseases such as those causing severe acute respiratory syndrome and Middle East respiratory syndrome, as well as devastating outbreaks of diseases caused by the Ebola, Marburg, Zika and Lassa fever viruses, to name only a few examples. Additionally, bacterial infections leading to bubonic and pneumonic plague, most notably in Madagascar in 2018, as well as malaria in many tropical countries, melioidosis in south east Asia and tularaemia in northern Europe and North America, have incurred significant morbidity and mortality. In this review series, the life cycle of these pathogens and the epidemiology of disease have been reviewed in the context of potential points of intervention for the prevention of human infection. Many of the emerging pathogens are zoonoses and, as such, there is scope for intervention at the animal/insect/environmental reservoir. Other pathogens covered in this review series are considered to be re-emerging, such as multi-drug resistant tuberculosis.
Topics: Animals; Bacterial Infections; Bacterial Vaccines; Communicable Diseases, Emerging; Disease Outbreaks; Flaviviridae Infections; Humans; Viral Vaccines
PubMed: 30993689
DOI: 10.1111/cei.13303 -
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