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Vaccines Aug 2022is the leading cause of global diarrheal deaths that currently lacks a licensed vaccine. Shigellosis drives antimicrobial resistance and leads to economic impact... (Review)
Review
is the leading cause of global diarrheal deaths that currently lacks a licensed vaccine. Shigellosis drives antimicrobial resistance and leads to economic impact through linear growth faltering. Today, there is a robust pipeline of vaccines in clinical development which are broadly divided into parenteral glycoconjugate vaccines, consisting of O-antigen conjugated to carrier proteins, and oral live attenuated vaccines, which incorporate targeted genetic mutations seeking to optimize the balance between reactogenicity, immunogenicity and ultimately protection. Proof of efficacy has previously been shown with both approaches but for various reasons no vaccine has been licensed to date. In this report, we outline the requirements for a vaccine and describe the current pipeline in the context of the many candidates that have previously failed or been abandoned. The report refers to papers from individual vaccine developers in this special supplement of which is focused on vaccines. Once readouts of safety and immunogenicity from current trials of lead candidate vaccines among the target population of young children in low- and middle-income countries are available, the likely time to licensure of a first vaccine will become clearer.
PubMed: 36146457
DOI: 10.3390/vaccines10091376 -
Current Opinion in Infectious Diseases Oct 2018Diarrhoea is a major global health problem, and recent studies have confirmed Shigella as a major contributor to this burden. Here, we review recent advances in Shigella... (Review)
Review
PURPOSE OF REVIEW
Diarrhoea is a major global health problem, and recent studies have confirmed Shigella as a major contributor to this burden. Here, we review recent advances in Shigella research; focusing on their epidemiology, pathogenesis, antimicrobial resistance, and the role of the gut microbiome during infection.
RECENT FINDINGS
Enhanced epidemiological data, combined with new generation diagnostics, has highlighted a greater burden of Shigella disease than was previously estimated, which is not restricted to vulnerable populations in low-middle income countries. As we gain an ever more detailed insight into the orchestrated mechanisms that Shigella exploit to trigger infection, we can also begin to appreciate the complex role of the gut microbiome in preventing and inducing such infections. The use of genomics, in combination with epidemiological data and laboratory investigations, has unravelled the evolution and spread of various species. Such measures have identified resistance to antimicrobials as a key contributor to the success of specific clones.
SUMMARY
We need to apply novel findings towards sustainable approaches for treating and preventing Shigella infections. Vaccines and alternative treatments are under development and may offer an opportunity to reduce the burden of Shigella disease and restrict the mobility of antimicrobial resistant clones.
Topics: Anti-Bacterial Agents; Antibiosis; Communicable Disease Control; Diarrhea; Dysentery, Bacillary; Gastrointestinal Microbiome; Global Health; Humans; Shigella; Shigella Vaccines
PubMed: 30048255
DOI: 10.1097/QCO.0000000000000475 -
International Journal of Molecular... Apr 2024Shigellosis is a severe gastrointestinal disease that annually affects approximately 270 million individuals globally. It has particularly high morbidity and mortality... (Review)
Review
Shigellosis is a severe gastrointestinal disease that annually affects approximately 270 million individuals globally. It has particularly high morbidity and mortality in low-income regions; however, it is not confined to these regions and occurs in high-income nations when conditions allow. The ill effects of shigellosis are at their highest in children ages 2 to 5, with survivors often exhibiting impaired growth due to infection-induced malnutrition. The escalating threat of antibiotic resistance further amplifies shigellosis as a serious public health concern. This review explores pathology, with a primary focus on the status of vaccine candidates. These candidates include killed whole-cells, live attenuated organisms, LPS-based, and subunit vaccines. The strengths and weaknesses of each vaccination strategy are considered. The discussion includes potential immunogens, such as LPS, conserved T3SS proteins, outer membrane proteins, diverse animal models used in vaccine research, and innovative vaccine development approaches. Additionally, this review addresses ongoing challenges that necessitate action toward advancing effective prevention and control measures.
Topics: Humans; Shigella Vaccines; Dysentery, Bacillary; Animals; Shigella; Vaccines, Subunit; Vaccine Development; Vaccines, Attenuated
PubMed: 38673913
DOI: 10.3390/ijms25084329 -
Reviews of Infectious Diseases 1989Shigellosis remains a major public health problem in developing countries. In these nations, the disease affects young children for the most part. The infecting organism... (Review)
Review
Shigellosis remains a major public health problem in developing countries. In these nations, the disease affects young children for the most part. The infecting organism causes illness by invading the colonic mucosa. It is closely related to nonpathogenic Escherichia coli, and genetic material can be transferred from one organism to the other, a process increasing the pathogenic potential of the E. coli or reducing the virulence of the strain of Shigella. Knowledge of the genetics of virulence of shigellae enables the construction of living, attenuated oral vaccines that may offer a practical means of controlling the disease.
Topics: Animals; Bacterial Vaccines; Dysentery, Bacillary; Humans; Shigella; Vaccines, Attenuated; Vaccines, Synthetic
PubMed: 2669098
DOI: 10.1093/clinids/11.supplement_3.s547 -
Vaccine Aug 2019PATH hosted the second Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference in Mexico City in June 2018, again providing experts from around... (Review)
Review
PATH hosted the second Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference in Mexico City in June 2018, again providing experts from around the world an opportunity to participate in a highly collaborative forum to discuss progress in the development of new enteric vaccines. Through a combination of plenary sessions and posters, keynote presentations, and workshops, the 2018 VASE Conference aimed to accelerate communication and progress among those working to achieve the goal of licensed vaccines against these two bacterial pathogens. Many presentations recognized the importance of diarrheal disease and long-term sequelae caused by infections with Shigella and enterotoxigenic E. coli (ETEC). Other presentations explored new strategies for vaccine development, including the search for novel, possibly conserved, antigens for more effective vaccines. Much progress is being made as some vaccine candidates are now moving through clinical trials. Research presented in oral and poster presentations at the VASE Conference covered a range of topics, including: the global burden of disease, epidemiology, and health economics; host parameters and genomics that predict responses to infection and disease; preclinical evaluations of vaccine antigens and models of enteric diseases; and vaccine candidates in clinical trials and human challenge studies. This article reviews key points and highlighted research presented in each of the plenary conference sessions and poster presentations at the 2018 VASE Conference.
Topics: Animals; Antigens, Bacterial; Clinical Trials as Topic; Congresses as Topic; Diarrhea; Disease Models, Animal; Dysentery, Bacillary; Enterotoxigenic Escherichia coli; Escherichia coli Infections; Escherichia coli Vaccines; Host-Pathogen Interactions; Humans; Immunization; Macaca mulatta; Mice; Shigella; Shigella Vaccines
PubMed: 31358236
DOI: 10.1016/j.vaccine.2019.02.070 -
Expert Review of Vaccines Oct 2006Several live-attenuated Shigella vaccines, with well-defined mutations in specific genes, have shown great promise in eliciting significant immune responses when given... (Review)
Review
Several live-attenuated Shigella vaccines, with well-defined mutations in specific genes, have shown great promise in eliciting significant immune responses when given orally to volunteers. These responses have been measured by evaluating antibody-secreting cells, serum antibody levels and fecal immunoglobulin A to bacterial lipopolysaccharide and to individual bacterial invasion plasmid antigens. In this review, data collected from volunteer trials with live Shigella vaccines from three different research groups are described. The attenuating features of the bacterial strains, as well as the immune response following the use of different dosing regimens, are also described. The responses obtained with each vaccine strain are compared with data obtained from challenge trials using wild-type Shigella strains. Although the exact correlates of protection have not been found, some consensus may be derived as to what may constitute a protective immune response. Future directions in the field of live Shigella vaccines are also discussed.
Topics: Adolescent; Adult; Animals; Child; Child, Preschool; Clinical Trials as Topic; Dysentery, Bacillary; Humans; Immunity, Innate; Immunization Schedule; Infant; Military Medicine; Shigella; Shigella Vaccines; United States; Vaccination; Vaccines, Attenuated
PubMed: 17181440
DOI: 10.1586/14760584.5.5.669 -
Vaccines Apr 2022We are at an exciting moment in time with the advancement of many vaccines, including a shigella vaccine for the world. It is instructive to look at the long road that... (Review)
Review
We are at an exciting moment in time with the advancement of many vaccines, including a shigella vaccine for the world. It is instructive to look at the long road that some vaccines have traveled to recognize the remarkable accomplishments of those who were pioneers, appreciate the evolution of scientific and applied technology, and inform the future history of a vaccine that would have great potential for global health. To achieve this valuable retrospective, a narrative historical literature review was undertaken utilizing PubMed and Embase databases with relevant search terms. Retrieved articles were reviewed and information was organized into historical themes, landmark discoveries, and important vaccine development parallels. The literature reviewed was synthesized into major eras of shigella vaccine development from pathogen discovery and first attempts to empirical approaches of killed whole-cell and live-attenuated approaches, and a modern era that applied recombinant DNA engineering and structural vaccinology. The history of shigella vaccine development has largely followed the evolutionary path of vaccine development over the last 120 years, but with important lessons learned that should be considered as we embark on the future chapters of bringing to the world a safe and effective vaccine for global health.
PubMed: 35632401
DOI: 10.3390/vaccines10050645 -
Lancet (London, England) Feb 2018Shigellosis is a clinical syndrome caused by invasion of the epithelium lining the terminal ileum, colon, and rectum by Shigella species. Although infections occur... (Review)
Review
Shigellosis is a clinical syndrome caused by invasion of the epithelium lining the terminal ileum, colon, and rectum by Shigella species. Although infections occur globally, and in people of all ages, endemic infections among children aged 1-4 years living in low-income and middle-income settings constitute most of the disease burden. The versatile manifestations of these highly contagious organisms range from acute watery diarrhoea to fulminant dysentery characterised by frequent scant bloody stools with fever, prostration, and abdominal cramps. A broad array of uncommon, but often severe, intestinal and extraintestinal complications can occur. Despite marked reductions in mortality during the past three decades, there are roughly 164 000 annual deaths attributable to shigellosis. Intercontinental dissemination of multiresistant shigella strains, facilitated by travellers and men who have sex with men, has prompted new recommendations for antibiotic therapy. Awareness of disease burden and the emerging threats posed by shigella have accelerated interest in development of shigella vaccines, many of which are being tested in clinical trials.
Topics: Adult; Child, Preschool; Dysentery, Bacillary; Endemic Diseases; Homosexuality, Male; Humans; Male; Shigella
PubMed: 29254859
DOI: 10.1016/S0140-6736(17)33296-8 -
The Lancet. Global Health Nov 2023Shigellosis causes considerable public health burden, leading to excess deaths as well as acute and chronic consequences, particularly among children living in... (Review)
Review
Shigellosis causes considerable public health burden, leading to excess deaths as well as acute and chronic consequences, particularly among children living in low-income and middle-income countries (LMICs). Several Shigella vaccine candidates are advancing in clinical trials and offer promise. Although multiple target populations might benefit from a Shigella vaccine, the primary strategic goal of WHO is to accelerate the development and accessibility of safe, effective, and affordable Shigella vaccines that reduce mortality and morbidity in children younger than 5 years living in LMICs. WHO consulted with regulators and policy makers at national, regional, and global levels to evaluate pathways that could accelerate regulatory approval in this priority population. Special consideration was given to surrogate efficacy biomarkers, the role of controlled human infection models, and the establishment of correlates of protection. A field efficacy study in children younger than 5 years in LMICs is needed to ensure introduction in this priority population.
Topics: Child; Humans; Shigella Vaccines; Developing Countries; Dysentery, Bacillary
PubMed: 37858591
DOI: 10.1016/S2214-109X(23)00421-7 -
Vaccine Mar 2024The global nonprofit organization PATH hosted the third Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference in Washington, DC, on November... (Review)
Review
The global nonprofit organization PATH hosted the third Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference in Washington, DC, on November 29 to December 1, 2022. With a combination of plenary sessions and posters, keynote presentations, and breakout workshops, the 2022 VASE Conference featured key updates on research related to the development of vaccines against neglected diarrheal pathogens including Shigella, enterotoxigenic Escherichia coli (ETEC), Campylobacter, and Salmonella. The presentations and discussions highlighted the significant impact of these diarrheal pathogens, particularly on the health of infants and young children in low- and middle-income countries, reflecting the urgent need for the development and licensure of new enteric vaccines. Oral and poster presentations at the VASE Conference explored a range of topics, including: the global burden and clinical presentation of disease, epidemiology, and the impact of interventions; the assessment of the value of vaccines against enteric pathogens; preclinical evaluations of vaccine candidates and models of enteric diseases; vaccine candidates in clinical trials and human challenge models; host parameters and genomics that predict responses to infection and disease; the application of new omics technologies for characterization of emerging pathogens and host responses; novel adjuvants, vaccine delivery platforms, and immunization strategies; and strategies for combination/co-administered vaccines. The conference agenda also featured ten breakout workshop sessions on topics of importance to the enteric vaccine field, which are summarized separately. This article reviews key points and highlighted research presented in each of the plenary conference sessions and poster presentations at the 2022 VASE Conference.
Topics: Humans; Diarrhea; Dysentery, Bacillary; Enterotoxigenic Escherichia coli; Escherichia coli Infections; Escherichia coli Vaccines; Oligopeptides; Shigella; Shigella Vaccines
PubMed: 38030421
DOI: 10.1016/j.vaccine.2023.11.031