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Vaccine May 2021Chlamydia trachomatis is the causative agent of a highly prevalent sexually transmitted bacterial disease and is associated with a number of severe disease... (Review)
Review
Chlamydia trachomatis is the causative agent of a highly prevalent sexually transmitted bacterial disease and is associated with a number of severe disease complications. Current therapy options are successful at treating disease, but patients are left without protective immunity and do not benefit the majority asymptomatic patients who do not seek treatment. As such, there is a clear need for a broad acting, protective vaccine that can prevent transmission and protect against symptomatic disease presentation. There are three key elements that underlie successful vaccine development: 1) Chlamydia biology and immune-evasion adaptations, 2) the correlates of protection that prevent disease in natural and experimental infection, 3) reflection upon the evidence provided by previous vaccine attempts. In this review, we give an overview of the unique intra-cellular biology of C. trachomatis and give insight into the dynamic combination of adaptations that allow Chlamydia to subvert host immunity and survive within the cell. We explore the current understanding of chlamydial immunity in animal models and in humans and characterise the key immune correlates of protection against infection. We discuss in detail the specific immune interactions involved in protection, with relevance placed on the CD4+ T lymphocyte and B lymphocyte responses that are key to pathogen clearance. Finally, we provide a timeline of C. trachomatis vaccine research to date and evaluate the successes and failures in development so far. With insight from these three key elements of research, we suggest potential solutions for chlamydial vaccine development and promising avenues for further exploration.
Topics: Animals; Bacterial Vaccines; CD4-Positive T-Lymphocytes; Chlamydia Infections; Chlamydia trachomatis; Humans; Vaccination
PubMed: 33771390
DOI: 10.1016/j.vaccine.2021.03.043 -
The Veterinary Clinics of North... Mar 2020Canine infectious respiratory disease complex (CIRDC) refers to a syndrome of diseases that can be caused by several different bacterial and viral pathogens. These... (Review)
Review
Canine infectious respiratory disease complex (CIRDC) refers to a syndrome of diseases that can be caused by several different bacterial and viral pathogens. These pathogens are often highly contagious, and coinfections are common. Clinical signs are frequently mild and self-limiting; however, some individual cases progress to severe disease. Clinical diagnosis of CIRDC is often based on history of exposure and physical examination findings; however, determining the etiologic agent requires application of specific diagnostic tests, and results can be difficult to interpret because of widespread subclinical infections.
Topics: Animals; Anti-Infective Agents; Bacterial Vaccines; Dog Diseases; Dogs; Respiratory Tract Infections; Viral Vaccines
PubMed: 31813556
DOI: 10.1016/j.cvsm.2019.10.009 -
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 -
Biomedicine & Pharmacotherapy =... Dec 2020Mucin 1 (MUC1) is a transmembrane mucin glycoprotein expressed on the surface of almost all epithelial cells. Aberrantly glycosylated MUC1 is associated with cellular... (Review)
Review
Mucin 1 (MUC1) is a transmembrane mucin glycoprotein expressed on the surface of almost all epithelial cells. Aberrantly glycosylated MUC1 is associated with cellular transformation from a normal to malignant phenotype in human cancers. Therefore, MUC1 is the major target for the design and development of cancer vaccines. MUC1-based cancer vaccines are a promising strategy for preventing cancer progression and metastasis. This review summarizes the most significant milestones achieved to date in the development of different MUC-1-based vaccine approaches in clinical trials. Further, it provides perspectives for future research that may promote clinical advances in infection-associated cancers.
Topics: Animals; Bacterial Infections; Bacterial Vaccines; Cancer Vaccines; Glycosylation; Humans; Immunization; Mucin-1; Neoplasms; Tumor Microenvironment; Tumor Virus Infections; Viral Vaccines
PubMed: 33113416
DOI: 10.1016/j.biopha.2020.110888 -
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 -
Current Topics in Microbiology and... 2020Vaccines are considered one of the most important advances in modern medicine and have greatly improved our quality of life by reducing or eliminating many serious... (Review)
Review
Vaccines are considered one of the most important advances in modern medicine and have greatly improved our quality of life by reducing or eliminating many serious infectious diseases. Successful vaccines have been developed against many of the most common human pathogens, and this success has not been dependent upon any one specific class of vaccine since subunit vaccines, non-replicating whole-virus or whole-bacteria vaccines, and attenuated live vaccines have all been effective for particular vaccine targets. After completing the initial immunization series, one common aspect of successful vaccines is that they induce long-term protective immunity. In contrast, several partially successful vaccines appear to induce protection that is relatively short-lived and it is likely that long-term protective immunity will be critical for making effective vaccines against our most challenging diseases such as AIDS and malaria.
Topics: Bacterial Vaccines; Humans; Quality of Life; Vaccines; Vaccines, Attenuated; Vaccines, Subunit; Vaccinology; Viral Vaccines
PubMed: 30046984
DOI: 10.1007/82_2018_102 -
Hematology. American Society of... Dec 2020An estimated 1 million people in the United States have functional or anatomic asplenia or hyposplenia. Infectious complications due to encapsulated organisms such as...
An estimated 1 million people in the United States have functional or anatomic asplenia or hyposplenia. Infectious complications due to encapsulated organisms such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae can lead to fulminant sepsis and death, particularly in young children, in the period shortly after splenectomy, and in immunocompromised patients. Patients with asplenia are also at risk for less common infections due to Capnocytophaga, Babesia, and malaria. Antibiotic prophylaxis, vaccines, and patient and family education are the mainstays of prevention in these at-risk patients. Recommendations for antibiotic prophylaxis typically target high-risk periods, such as 1 to 3 years after splenectomy, children ≤5 years of age, or patients with concomitant immunocompromise. However, the risk for sepsis is lifelong, with infections occurring as late as 40 years after splenectomy. Currently available vaccines recommended for patients with asplenia include pneumococcal vaccines (13-valent pneumococcal conjugate vaccine followed by the 23-valent pneumococcal polysaccharide vaccine), meningococcal vaccines (meningococcal conjugate vaccines for serogroups A, C, Y and W-135 and serogroup B meningococcal vaccines), H. influenzae type b vaccines, and inactivated influenza vaccines. Ongoing booster doses are also recommended for pneumococcal and meningococcal vaccines to maintain protection. Despite the availability of prevention tools, adherence is often a challenge. Dedicated teams or clinics focused on patient education and monitoring have demonstrated substantial improvements in vaccine coverage rates for individuals with asplenia and reduced risk of infection. Future efforts to monitor the quality of care in patients with asplenia may be important to bridge the know-do gap in this high-risk population.
Topics: Adult; Anti-Bacterial Agents; Bacterial Capsules; Bacterial Infections; Child; Haemophilus Vaccines; Humans; Infection Control; Infections; Meningococcal Vaccines; Pneumococcal Vaccines; Primary Immunodeficiency Diseases; Spleen; Splenectomy; Vaccination
PubMed: 33275684
DOI: 10.1182/hematology.2020000117