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Current Opinion in Immunology Dec 2023Shigella spp. are major causative agents of bacillary dysentery, a severe enteric disease characterized by destruction and inflammation of the colonic epithelium... (Review)
Review
Shigella spp. are major causative agents of bacillary dysentery, a severe enteric disease characterized by destruction and inflammation of the colonic epithelium accompanied by acute diarrhea, fever, and abdominal pain. Although antibiotics have traditionally been effective, the prevalence of multidrug-resistant strains is increasing, stressing the urgent need for a vaccine. The human-specific nature of shigellosis and the absence of a dependable animal model have posed significant obstacles in understanding Shigella pathogenesis and the host immune response, both of which are crucial for the development of an effective vaccine. Efforts have been made over time to develop a physiological model that mimics the pathological features of the human disease with limited success until the recent development of genetically modified mouse models. In this review, we provide an overview of Shigella pathogenesis and chronicle the historical development of various shigellosis models, emphasizing their strengths and weaknesses.
Topics: Animals; Mice; Humans; Dysentery, Bacillary; Shigella; Inflammation; Disease Models, Animal; Vaccines
PubMed: 37952487
DOI: 10.1016/j.coi.2023.102399 -
Human Vaccines & Immunotherapeutics 2015Diarrheal diseases remain a leading cause of global childhood mortality and morbidity. Several recent epidemiological studies highlight the rate of diarrheal diseases in... (Review)
Review
Diarrheal diseases remain a leading cause of global childhood mortality and morbidity. Several recent epidemiological studies highlight the rate of diarrheal diseases in different parts of the world and draw attention to the impact on childhood growth and survival. Despite the well-documented global burden of diarrheal diseases, currently there are no combination diarrheal vaccines, only licensed vaccines for rotavirus and cholera, and Salmonella typhi-based vaccines for typhoid fever. The recognition of the impact of diarrheal episodes on infant growth, as seen in resource-poor countries, has spurred action from governmental and non-governmental agencies to accelerate research toward affordable and effective vaccines against diarrheal diseases. Both travelers and children in endemic countries will benefit from a combination diarrheal vaccine, but it can be argued that the greater proportion of any positive impact will be on the public health status of the latter. The history of combination pediatric vaccines indicate that monovalent or single disease vaccines are typically licensed first prior to formulation in a combination vaccine, and that the combinations themselves undergo periodic revision in response to need for improvement in safety or potential for wider coverage of important pediatric pathogens. Nevertheless combination pediatric vaccines have proven to be an effective tool in limiting or eradicating communicable childhood diseases worldwide. The landscape of diarrheal vaccine candidates indicates that there now several in active development that offer options for potential testing of combinations to combat those bacterial and viral pathogens responsible for the heaviest disease burden-rotavirus, ETEC, Shigella, Campylobacter, V. cholera and Salmonella.
Topics: Bacterial Vaccines; Campylobacter; Diarrhea; Global Health; Humans; Rotavirus; Salmonella typhi; Shigella; Vaccines, Combined; Viral Vaccines
PubMed: 25891647
DOI: 10.4161/21645515.2014.986984 -
Vaccine Aug 2019The mortality and morbidity burden estimation of diarrheal diseases (DD), and Shigella and Enterotoxigenic E. Coli (ETEC) varies among different studies and by the... (Review)
Review
The mortality and morbidity burden estimation of diarrheal diseases (DD), and Shigella and Enterotoxigenic E. Coli (ETEC) varies among different studies and by the models used for producing these estimates. Understanding the real burden of these important pathogens will guide public health and policy makers to prioritize resources for accelerating interventions against these enteric infections. In addition, long term effects, in the form of growth faltering, cognitive impairment and decreased school performance are important aspects of burden that has not been well captured. Efforts to incorporate these effects and refine their estimation, in the form of Disability Adjusted Life years (DALYs) are very important to inform the burden of diarrheal diseases and Shigella and ETEC specifically. The Institute for Health Metrics and Evaluation (IHME) at the University of Washington conducted a workshop at the VASE 2018 meeting to discuss IHME Global Burden of Diseases (GBD) modelling methods for diarrheal diseases, with a focus on ETEC and Shigella estimates in relation to other pathogens, including limitations, areas of improvements, and IHME plans for future GBD iterations.
Topics: Child; Child, Preschool; Congresses as Topic; Diarrhea; Dysentery, Bacillary; Enterotoxigenic Escherichia coli; Escherichia coli Infections; Escherichia coli Vaccines; Humans; Immunization; Models, Statistical; Quality-Adjusted Life Years; Shigella; Shigella Vaccines; Survival Analysis
PubMed: 30711317
DOI: 10.1016/j.vaccine.2019.01.031 -
BMC Public Health 2013Diarrhea is a leading cause of mortality in children under 5 years along with its long-term impact on growth and cognitive development. Despite advances in the... (Review)
Review
BACKGROUND
Diarrhea is a leading cause of mortality in children under 5 years along with its long-term impact on growth and cognitive development. Despite advances in the understanding of diarrheal disorders and management strategies, globally nearly 750,000 children die annually as a consequence of diarrhea.
METHODS
We conducted a systematic review of the efficacy and effectiveness studies. We used a standardized abstraction and grading format and performed meta-analyses for all outcomes. The estimated effect of cholera, shigella, Enterotoxigenic Escherichia coli (ETEC) and rotavirus vaccines was determined by applying the standard Child Health Epidemiology Reference Group (CHERG) rules.
RESULTS
A total of 24 papers were selected and analyzed for all the four vaccines. Based on the evidence, we propose a 74% mortality reduction in rotavirus specific mortality, 52% reduction in cholera incidence due to their respective vaccines. We did not find sufficient evidence and a suitable outcome to project mortality reductions for cholera, ETEC and shigella in children under 5 years.
CONCLUSION
Vaccines for rotavirus and cholera have the potential to reduce diarrhea morbidity and mortality burden. But there is no substantial evidence of efficacy for ETEC and shigella vaccines, although several promising vaccine concepts are moving from the development and testing pipeline towards efficacy and Phase 3 trials.
Topics: Bacterial Vaccines; Child; Child, Preschool; Cholera; Cholera Vaccines; Comorbidity; Diarrhea; Dysentery; Dysentery, Bacillary; Escherichia coli Infections; Humans; Immunization Schedule; Infant; Male; Rotavirus Infections; Shigella Vaccines; Viral Vaccines
PubMed: 24564510
DOI: 10.1186/1471-2458-13-S3-S11 -
Microorganisms Jun 2021The global diarrheal disease burden for , enterotoxigenic (ETEC), and is estimated to be 88M, 75M, and 75M cases annually, respectively. A vaccine against this target... (Review)
Review
The global diarrheal disease burden for , enterotoxigenic (ETEC), and is estimated to be 88M, 75M, and 75M cases annually, respectively. A vaccine against this target trio of enteric pathogens could address about one-third of diarrhea cases in children. All three of these pathogens contribute to growth stunting and have demonstrated increasing resistance to antimicrobial agents. Several combinations of antigens are now recognized that could be effective for inducing protective immunity against each of the three target pathogens in a single vaccine for oral administration or parenteral injection. The vaccine combinations proposed here would result in a final product consistent with the World Health Organization's (WHO) preferred product characteristics for ETEC and vaccines, and improve the vaccine prospects for support from Gavi, the Vaccine Alliance, and widespread uptake by low- and middle-income countries' (LMIC) public health stakeholders. Broadly protective antigens will enable multi-pathogen vaccines to be efficiently developed and cost-effective. This review describes how emerging discoveries for each pathogen component of the target trio could be used to make vaccines, which could help reduce a major cause of poor health, reduced cognitive development, lost economic productivity, and poverty in many parts of the world.
PubMed: 34202102
DOI: 10.3390/microorganisms9071382 -
Vaccine Aug 2019Catalyzing and sustaining momentum for long-term research investments can be a challenge, especially for enteric pathogens like ETEC andShigella that are most... (Review)
Review
Catalyzing and sustaining momentum for long-term research investments can be a challenge, especially for enteric pathogens like ETEC andShigella that are most threatening to the health of children in low-resource areas, and whose vaccines would not be for global use. The 2018 Vaccines Against Shigella and ETEC (VASE) Conference included a workshop focused on building the capacity of scientists to communicate about their own research and advocate for additional attention and funding for enteric disease and vaccines research. Workshop presenters shared best practices and examples of advocacy, communications, and messaging tactics that have been used successfully during early stages of vaccine development research for other pathogens. The presentations were followed by an interactive, hands-on training for real-life communication opportunities for scientists that could result in increased research funding, including developing resonant messaging for relevant audiences and practicing interviews.
Topics: Consumer Advocacy; Developing Countries; Diarrhea; Dysentery, Bacillary; Enterotoxigenic Escherichia coli; Escherichia coli Infections; Escherichia coli Vaccines; Fund Raising; Humans; Immunization; Shigella; Shigella Vaccines
PubMed: 30737042
DOI: 10.1016/j.vaccine.2018.12.033 -
PLoS Neglected Tropical Diseases May 2020Salmonella and Shigella species are food- and water-borne pathogens that are responsible for enteric infections in both humans and animals and are still the major cause...
Salmonella and Shigella species are food- and water-borne pathogens that are responsible for enteric infections in both humans and animals and are still the major cause of morbidity and mortality in the emerging countries. The existence of multiple Salmonella and Shigella serotypes as well as the emergence of strains resistant to antibiotics require the development of broadly protective therapies. Those bacteria utilize a Type III Secretion System (T3SS), necessary for their pathogenicity. The structural proteins composing the T3SS are common to all virulent Salmonella and Shigella spp., particularly the needle-tip proteins SipD (Salmonella) and IpaD (Shigella). We investigated the immunogenicity and protective efficacy of SipD and IpaD administered by intranasal and intragastric routes, in a mouse model of Salmonella enterica serotype Typhimurium (S. Typhimurium) intestinal challenge. Robust IgG (in all immunization routes) and IgA (in intranasal and oral immunization routes) antibody responses were induced against both proteins. Mice immunized with SipD or IpaD were protected against lethal intestinal challenge with S. Typhimurium or Shigella flexneri (100 Lethal Dose 50%). We have shown that SipD and IpaD are able to induce a cross-protection in a murine model of infection by Salmonella and Shigella. We provide the first demonstration that Salmonella and Shigella T3SS SipD and IpaD are promising antigens for the development of a cross-protective Salmonella-Shigella vaccine. These results open the way to the development of cross-protective therapeutic molecules.
Topics: Administration, Intranasal; Administration, Oral; Animals; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Proteins; Cross Protection; Disease Models, Animal; Dysentery, Bacillary; Female; Immunoglobulin A; Immunoglobulin G; Membrane Proteins; Mice, Inbred BALB C; Salmonella Infections; Salmonella Vaccines; Salmonella typhimurium; Shigella Vaccines; Shigella flexneri; Survival Analysis
PubMed: 32463817
DOI: 10.1371/journal.pntd.0008326 -
Vaccine Aug 2019Well-established, validated and clinically meaningful primary and secondary endpoints are critical in advancing vaccines through proof of principal studies, licensure... (Review)
Review
Well-established, validated and clinically meaningful primary and secondary endpoints are critical in advancing vaccines through proof of principal studies, licensure and pre-qualification. To that end, the field of vaccine development for Shigella, enterotoxigenic Escherichia coli (ETEC) as well as other enteric pathogens would benefit greatly from a focused review of clinical endpoints and the use of common endpoints across the field to enable study-to-study comparisons as well as comparative assessments between vaccine candidates. A workshop was conducted to review clinical endpoints from controlled human challenge studies, field studies in naïve adult travelers and pediatric studies in low-middle income countries and to develop a consensus on clinical endpoints for future vaccine trials. Following sequential presentations on different study designs (CHIM, travelers' efficacy and pediatric efficacy), workshop participants broke into three simultaneous workgroups focused on those study designs to discuss a number of topics key to clinical endpoints specific to each study design. Previously utilized endpoints were reviewed with an eye towards potentially novel endpoints for future studies and consideration of the disease parameters and spectrum of disease targeted for prevention. The strength of support among workshop participants for the use of various endpoints is summarized as are recommendations for additional endpoints to be considered in future studies. It is anticipated that this report will facilitate endpoint determination in future efficacy trials of vaccine candidates.
Topics: Adult; Child, Preschool; Clinical Trials as Topic; Congresses as Topic; Developing Countries; Diarrhea; Dysentery, Bacillary; Endpoint Determination; Enterotoxigenic Escherichia coli; Escherichia coli Infections; Escherichia coli Vaccines; Humans; Immunization; Immunogenicity, Vaccine; Models, Immunological; Shigella; Shigella Vaccines; Travel
PubMed: 30981626
DOI: 10.1016/j.vaccine.2019.03.051 -
Vaccine Jun 2016Shigella are gram-negative bacteria that cause severe diarrhea and dysentery. In 2013, Shigella infections caused an estimated 34,400 deaths in children less than five... (Review)
Review
Shigella are gram-negative bacteria that cause severe diarrhea and dysentery. In 2013, Shigella infections caused an estimated 34,400 deaths in children less than five years old and, in 2010, an estimated 40,000 deaths in persons older than five years globally. New disease burden estimates from newly deployed molecular diagnostic assays with increased sensitivity suggest that Shigella-associated morbidity may be much greater than previous disease estimates from culture-based methods. Primary prevention of this disease should be based on universal provision of potable water and sanitation methods and improved personal and food hygiene. However, an efficacious and low-cost vaccine would complement and accelerate disease reduction while waiting for universal access to water, sanitation, and hygiene improvements. This review article provides a landscape of Shigella vaccine development efforts. No vaccine is yet available, but human and animal challenge-rechallenge trials with virulent Shigella as well as observational studies in Shigella-endemic areas have shown that the incidence of disease decreases following Shigella infection, pointing to biological feasibility of a vaccine. Immunity to Shigella appears to be strain-specific, so a vaccine that covers the most commonly detected strains (i.e., S. flexneri 2a, 3a, 6, and S. sonnei) or a vaccine using cross-species conserved antigens would likely be most effective. Vaccine development and testing may be accelerated by use of animal models, such as the guinea pig keratoconjunctivitis or murine pneumonia models. Because there is no correlate of protection, however, human studies will be necessary to evaluate vaccine efficacy prior to deployment. A diversity of Shigella vaccine constructs are under development, including live attenuated, formalin-killed whole-cell, glycoconjugate, subunit, and novel antigen vaccines (e.g., Type III secretion system and outer membrane proteins).
Topics: Animals; Biomedical Research; Clinical Trials as Topic; Diarrhea; Disease Models, Animal; Dysentery, Bacillary; Humans; Shigella; Shigella Vaccines; Vaccines, Conjugate; Vaccines, Subunit
PubMed: 26979135
DOI: 10.1016/j.vaccine.2016.02.075 -
International Journal of Molecular... Feb 2023Shigellosis causes more than 200,000 deaths worldwide and most of this burden falls on Low- and Middle-Income Countries (LMICs), with a particular incidence in children... (Review)
Review
Shigellosis causes more than 200,000 deaths worldwide and most of this burden falls on Low- and Middle-Income Countries (LMICs), with a particular incidence in children under 5 years of age. In the last decades, has become even more worrisome because of the onset of antimicrobial-resistant strains (AMR). Indeed, the WHO has listed as one of the priority pathogens for the development of new interventions. To date, there are no broadly available vaccines against shigellosis, but several candidates are being evaluated in preclinical and clinical studies, bringing to light very important data and information. With the aim to facilitate the understanding of the state-of-the-art of vaccine development, here we report what is known about epidemiology and pathogenesis with a focus on virulence factors and potential antigens for vaccine development. We discuss immunity after natural infection and immunization. In addition, we highlight the main characteristics of the different technologies that have been applied for the development of a vaccine with broad protection against .
Topics: Child; Humans; Child, Preschool; Shigella Vaccines; Dysentery, Bacillary; Shigella; Virulence Factors; Anti-Infective Agents
PubMed: 36902092
DOI: 10.3390/ijms24054649