-
Human Vaccines & Immunotherapeutics Dec 2023The ongoing COVID-19 pandemic highlights that complications and mortality associated with infectious diseases increase with age. Various vaccines are recommended for... (Review)
Review
The ongoing COVID-19 pandemic highlights that complications and mortality associated with infectious diseases increase with age. Various vaccines are recommended for adults, but coverage rates remain suboptimal. Although co-administration would improve vaccine uptake and timely immunization, this is not routine practice in adults. We review key data on co-administration of vaccines in children and adults to reassure healthcare providers about its safety and advantages. In European countries and the United States, combined tetanus, diphtheria, and acellular pertussis boosters as well as meningococcal and human papillomavirus vaccines are recommended for healthy adolescents and adults of certain ages. Vaccination against influenza (annually), pneumococcal disease, and herpes zoster is recommended for older adults and specific risk groups. While co-administration is well established in children, it is less common in adults. Travelers can also receive multiple co-administered vaccines. Pediatric and travel vaccine co-administration has a well-established positive benefit-risk profile and is an efficient and cost-saving strategy to improve coverage. Healthcare providers could more often recommend and practice vaccine co-administration; this would not risk patient safety and health, would improve protection against vaccine-preventable diseases, and would help comply with national vaccination calendars. Recommending bodies may consider revising vaccination schedules to reduce the number of visits.
Topics: Adolescent; Humans; Child; United States; Aged; Vaccination Coverage; Pandemics; COVID-19; Vaccination; Tetanus Toxoid; Diphtheria-Tetanus-acellular Pertussis Vaccines
PubMed: 37039318
DOI: 10.1080/21645515.2023.2195786 -
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 -
Vaccine Nov 2023Shigella is the leading bacterial cause of diarrhoea and the second leading cause of diarrhoeal mortality among all ages. It also exhibits increasing levels of...
Shigella is the leading bacterial cause of diarrhoea and the second leading cause of diarrhoeal mortality among all ages. It also exhibits increasing levels of antibiotic resistance. The greatest burden is among children under five in low- and middle-income countries (LMICs). As such, a priority strategic goal of the World Health Organization (WHO) is the development of a safe, effective and affordable vaccine to reduce morbidity and mortality from Shigella-attributable dysentery and diarrhea, including long term outcomes associated with chronic inflammation and growth faltering, in children under 5 years of age in LMICs. In addition, a safe and effective Shigella vaccine is of potential interest to travellers and military both to prevent acute disease and rarer, long-term sequelae. An effective Shigella vaccine is also anticipated to reduce antibiotic use and thereby help diminish further emergence of enteric pathogens resistant to antimicrobials. The most advanced vaccine candidates are multivalent, parenteral formulations in Phase 2 and Phase 3 clinical studies. They rely on O-antigen-polysaccharide protein conjugate technologies or, alternatively, outer membrane vesicles expressing penta-acylated lipopolysaccharide that has been detoxified. Other parenteral and oral formulations, many delivering a broader array of Shigella antigens, are at earlier stages of clinical development. These formulations are being assessed in alignment with the WHO Preferred Product Characteristics, which call for a 1 to 2 dose primary immunization series given during the first 12 months of life, ideally starting at 6 months of age. This 'Vaccine Value Profile' (VVP) for Shigella is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, government agencies and multi-lateral organizations. All contributors have extensive expertise on various elements of the Shigella VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.
Topics: Child, Preschool; Humans; Diarrhea; Dysentery, Bacillary; Escherichia coli Infections; Shigella; Shigella Vaccines; Infant
PubMed: 37827969
DOI: 10.1016/j.vaccine.2022.12.037 -
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 -
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 Jul 2023There is a need for vaccines effective against shigella infection in young children in resource-limited areas. Protective immunity against shigella infection targets the...
There is a need for vaccines effective against shigella infection in young children in resource-limited areas. Protective immunity against shigella infection targets the O-specific polysaccharide (OSP) component of lipopolysaccharide. Inducing immune responses to polysaccharides in young children can be problematic, but high level and durable responses can be induced by presenting polysaccharides conjugated to carrier proteins. An effective shigella vaccine will need to be multivalent, targeting the most common global species and serotypes such as Shigella flexneri 2a, S. flexneri 3a, S. flexneri 6, and S. sonnei. Here we report the development of shigella conjugate vaccines (SCV) targeting S. flexneri 2a (SCV-Sf2a) and 3a (SCV-Sf3a) using squaric acid chemistry to result in single point sun-burst type display of OSP from carrier protein rTTHc, a 52 kDa recombinant protein fragment of the heavy chain of tetanus toxoid. We confirmed structure and demonstrated that these conjugates were recognized by serotype-specific monoclonal antibodies and convalescent sera of humans recovering from shigellosis in Bangladesh, suggesting correct immunological display of OSP. We vaccinated mice and found induction of serotype-specific OSP and LPS IgG responses, as well as rTTHc-specific IgG responses. Vaccination induced serotype-specific bactericidal antibody responses against S. flexneri, and vaccinated animals were protected against keratoconjunctivitis (Sereny test) and intraperitoneal challenge with virulent S. flexneri 2a and 3a, respectively. Our results support further development of this platform conjugation technology in the development of shigella conjugate vaccines for use in resource-limited settings.
Topics: Humans; Child; Animals; Mice; Child, Preschool; Shigella Vaccines; Shigella flexneri; Vaccines, Conjugate; Dysentery, Bacillary; Shigella; Lipopolysaccharides; O Antigens; Antibodies, Bacterial; Immunoglobulin G
PubMed: 37400283
DOI: 10.1016/j.vaccine.2023.06.052 -
Frontiers in Molecular Biosciences 2023Shigellosis is leading bacterial cause of diarrhea with high prevalence in children younger than 5 years in low- and middle-income countries, and increasing number of...
Shigellosis is leading bacterial cause of diarrhea with high prevalence in children younger than 5 years in low- and middle-income countries, and increasing number of reports of cases associated to anti-microbial resistance. No vaccines against are still licensed, but different candidates based on the O-antigen portion of lipopolysaccharides are in clinic. Generalized Modules for Membrane Antigens (GMMA) have been proposed as an alternative delivery system for the O-antigen, and a 4-component vaccine candidate (altSonflex1-2-3), containing GMMA from and 1b, 2a and 3a is being tested in a phase 1/2 clinical trial, with the aim to elicit broad protection against the most prevalent serotypes. Here, the 4-component GMMA vaccine candidate has been compared to a more traditional glycoconjugate formulation for the ability to induce functional antibodies in mice and rabbits. In mice, in the absence of Alhydrogel, GMMA induce higher IgG antibodies than glycoconjugates and stronger bactericidal titers against all serotypes. In the presence of Alhydrogel, GMMA induce O-antigen specific IgG levels similar to traditional glycoconjugates, but with a broader range of IgG subclasses, resulting in stronger bactericidal activity. In rabbits, GMMA elicit higher functional antibodies than glycoconjugates against , and similar responses to 1b, 2a and 3a, independently from the presence of Alhydrogel. Different O-antigen based vaccines against are now in clinical stage and it will be of particular interest to understand how the preclinical findings in the different animal models translate in humans.
PubMed: 38046812
DOI: 10.3389/fmolb.2023.1284515 -
Gastroenterology Research and Practice 2023To estimate gastroenteritis disease and its etiological agents in children under the age of 5 years living in South Africa. (Review)
Review
OBJECTIVE
To estimate gastroenteritis disease and its etiological agents in children under the age of 5 years living in South Africa.
METHODS
A mini literature review of pertinent articles published in ScienceDirect, PubMed, GoogleScholar, and Scopus was conducted using search terms: "Gastroenteritis in children," "Gastroenteritis in the world," Gastroenteritis in South Africa," "Prevalence of gastroenteritis," "Epidemiological surveillance of gastroenteritis in the world," and "Causes of gastroenteritis".
RESULTS
A total of 174 published articles were included in this mini review. In the last 20 years, the mortality rate resulting from diarrhea in children under the age of 5 years has declined and this is influenced by improved hygiene practices, awareness programs, an improved water and sanitation supply, and the availability of vaccines. More modern genomic amplification techniques were used to re-analyze stool specimens collected from children in eight low-resource settings in Asia, South America, and Africa reported improved sensitivity of pathogen detection to about 65%, that viruses were the main etiological agents in patients with diarrhea aged from 0 to 11 months but that , followed by sapovirus and enterotoxigenic had a high incidence in children aged 12-24 months. In addition, co-infections were noted in nearly 10% of diarrhea cases, with rotavirus and being the main co-infecting agents together with adenovirus, enteropathogenic , , or .
CONCLUSIONS
This mini review outlines the epidemiology and trends relating to parasitic, viral, and bacterial agents responsible for gastroenteritis in children in South Africa. An increase in sequence-independent diagnostic approaches will improve the identification of pathogens to resolve undiagnosed cases of gastroenteritis. Emerging state and national surveillance systems should focus on improving the identification of gastrointestinal pathogens in children and the development of further vaccines against gastrointestinal pathogens.
PubMed: 37663241
DOI: 10.1155/2023/1906782 -
Vaccine: X Dec 2023is the leading bacterial cause of diarrheal mortality in children and can cause long-term effects on growth and development. No licensed vaccines currently exist but...
BACKGROUND
is the leading bacterial cause of diarrheal mortality in children and can cause long-term effects on growth and development. No licensed vaccines currently exist but several promising candidates are in development and could be available in the next five years. Despite being a well-known public health target of the World Health Organization for decades, given current burden estimates and competing preventable disease priorities in low-income settings, whether the availability of an effective vaccine will lead to its prioritization and widespread introduction among countries at highest risk is unknown.
METHODS
We conducted a mixed-methods study of national stakeholders and healthcare providers in five countries in Asia and Africa and regional stakeholders in the Pan American Health Organization to identify preferences and priorities for forthcoming vaccines.
RESULTS
In our study of 89 individuals, diarrhea was the most frequently mentioned serious health concern for children under five years. Antimicrobial resistance (AMR) was more often considered very concerning than diarrhea or stunting. awareness was high but not considered a serious health concern by most stakeholders. Most participants were willing to consider adding a new vaccine to the routine immunization schedule but expressed reservations about a vaccine because of lower perceived burden relative to other preventable diseases and an already crowded schedule; interest was highest among national stakeholders in countries receiving more financial support for immunization. The priority of a vaccine rose when participants considered vaccine impacts on reducing stunting and AMR. Participants strongly preferred oral and combination vaccines compared to injectable and a single-antigen presentations, citing greater perceived community acceptability.
CONCLUSIONS
This study provides a critical opportunity to hear directly from country and regional stakeholders about health priorities and preferences around new vaccines. These findings should inform ongoing vaccine development efforts and eventual vaccine introduction and implementation planning.
PubMed: 37636544
DOI: 10.1016/j.jvacx.2023.100368 -
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