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Human Vaccines & Immunotherapeutics 2019Invasive non-typhoidal (iNTS) disease has emerged as a major public health concern. Yet, understanding of the global burden is incomplete, limited particularly by the... (Review)
Review
Invasive non-typhoidal (iNTS) disease has emerged as a major public health concern. Yet, understanding of the global burden is incomplete, limited particularly by the breadth of blood culture-based surveillance systems that are able to accurately diagnose the etiology of bacteremia. The accessibility of whole genome sequencing has allowed for genetic characterization of pathogens, shedding light on its evolutionary history and sounding alerts for its future progression. iNTS disease is observed to be a particular threat in sub-Saharan Africa, with a case fatality rate greatly exceeding that of typhoid fever, and commonly affecting infants, young children and immunocompromised adults. While iNTS disease might also be a threat in Asia and Latin America, its burden is not well characterized, primarily owing to the lack of comprehensive reporting in these regions. Drug-resistant serovars (e.g. Typhimurium sequence type 313 (ST313)) have emerged as a potential consequence of sustained antibiotic pressure. Genetic analyses have identified distinguished iNTS disease-causing strains that are particularly virulent in certain human host populations. Effective treatment strategies, including vaccination, are necessary; iNTS vaccines targeting the most common serovars, Typhimurium, Enteritidis and Dublin, are currently in early developmental stages. Funding and political support is needed to promote vaccine development and implementation programs to ultimately reduce the threat of iNTS disease in high risk areas.
Topics: Anti-Bacterial Agents; Bacteremia; Cost of Illness; Drug Resistance, Bacterial; Global Health; Humans; Immunocompromised Host; Salmonella Infections; Salmonella Vaccines; Salmonella enterica; Vaccination; Whole Genome Sequencing
PubMed: 30081708
DOI: 10.1080/21645515.2018.1504717 -
Clinical and Vaccine Immunology : CVI Sep 2016Nontyphoidal Salmonella (NTS; i.e., Salmonella enterica organisms that do not cause typhoid or paratyphoid) are responsible for 94 million infections and 155,000 deaths... (Review)
Review
Nontyphoidal Salmonella (NTS; i.e., Salmonella enterica organisms that do not cause typhoid or paratyphoid) are responsible for 94 million infections and 155,000 deaths worldwide annually, 86% of which are estimated to be foodborne. Although more than 50 serogroups and 2,600 serovars have been described, not all Salmonella serovars cause disease in humans and animals. Efforts are being made to develop NTS vaccines, with most approaches eliciting protection against serovars Typhimurium and Enteritidis (serogroups B [O:4] and D [O:9], respectively), as they are widely considered the most prevalent. Here, we show that serogroup C (O:6,7, O:6,8, or O:8 epitopes) is the most common serogroup in the United States, and the prevalence of serovars from this serogroup has been increasing in Europe and the United States over the last decade. They are also the most commonly isolated serovars from healthy cattle and poultry, indicating the underlying importance of surveillance in animals. Four out of the 10 most lethal serovars in the United States are serogroup C, and reports from African countries suggest that strains within this serogroup are highly antibiotic resistant. Serogroup C consists of highly diverse organisms among which 37 serovars account for the majority of human cases, compared to 17 and 11 serovars for serogroups B and D, respectively. Despite these concerning data, no human vaccines targeting serogroup C NTS are available, and animal vaccines are in limited use. Here, we describe the underestimated burden represented by serogroup C NTS, as well as a discussion of vaccines that target these pathogens.
Topics: Animals; Cattle; Cost of Illness; Global Health; Humans; Poultry; Prevalence; Salmonella; Salmonella Infections; Salmonella Infections, Animal; Salmonella Vaccines; Serogroup
PubMed: 27413069
DOI: 10.1128/CVI.00243-16 -
Human Vaccines & Immunotherapeutics 2014Though primarily enteric pathogens, Salmonellae are responsible for a considerable yet under-appreciated global burden of invasive disease. In South and South-East Asia,... (Review)
Review
Though primarily enteric pathogens, Salmonellae are responsible for a considerable yet under-appreciated global burden of invasive disease. In South and South-East Asia, this manifests as enteric fever caused by serovars Typhi and Paratyphi A. In sub-Saharan Africa, a similar disease burden results from invasive nontyphoidal Salmonellae, principally serovars Typhimurium and Enteritidis. The existing Ty21a live-attenuated and Vi capsular polysaccharide vaccines target S. Typhi and are not effective in young children where the burden of invasive Salmonella disease is highest. After years of lack of investment in new Salmonella vaccines, recent times have seen increased interest in the area led by emerging-market manufacturers, global health vaccine institutes and academic partners. New glycoconjugate vaccines against S. Typhi are becoming available with similar vaccines against other invasive serovars in development. With other new vaccines under investigation, including live-attenuated, protein-based and GMMA vaccines, now is an exciting time for the Salmonella vaccine field.
Topics: Africa South of the Sahara; Asia; Drug Discovery; Humans; Salmonella Infections; Salmonella Vaccines
PubMed: 24804797
DOI: 10.4161/hv.29054 -
Vaccine Jun 2015Salmonella enterica serovar Typhi produces significant morbidity and mortality worldwide despite the fact that there are licensed Salmonella Typhi vaccines available.... (Review)
Review
Salmonella enterica serovar Typhi produces significant morbidity and mortality worldwide despite the fact that there are licensed Salmonella Typhi vaccines available. This is primarily due to the fact that these vaccines are not used in the countries that most need them. There is growing recognition that an effective invasive Salmonella vaccine formulation must also prevent infection due to other Salmonella serovars. We anticipate that a multivalent vaccine that targets the following serovars will be needed to control invasive Salmonella infections worldwide: Salmonella Typhi, Salmonella Paratyphi A, Salmonella Paratyphi B (currently uncommon but may become dominant again), Salmonella Typhimurium, Salmonella Enteritidis and Salmonella Choleraesuis (as well as other Group C Salmonella). Live attenuated vaccines are an attractive vaccine formulation for use in developing as well as developed countries. Here, we describe the methods of attenuation that have been used to date to create live attenuated Salmonella vaccines and provide an update on the progress that has been made on these vaccines.
Topics: Africa; Antibodies, Bacterial; Asia; Humans; Salmonella; Salmonella Infections; Salmonella Vaccines; Salmonella paratyphi A; Salmonella typhi; Salmonella typhimurium; Serogroup; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccines, Attenuated
PubMed: 25902362
DOI: 10.1016/j.vaccine.2015.04.029 -
Current Opinion in Infectious Diseases Oct 2017We searched PubMed for scientific literature published in the past 2 years for relevant information regarding the burden of invasive nontyphoidal Salmonella disease and... (Review)
Review
PURPOSE OF REVIEW
We searched PubMed for scientific literature published in the past 2 years for relevant information regarding the burden of invasive nontyphoidal Salmonella disease and host factors associated with nontyphoidal Salmonella infection and discuss current knowledge on vaccine development. The following search terms were used: Salmonella, non typhoidal/nontyphoidal, NTS, disease, bloodstream infection, invasive, sepsis/septicaemia/septicemia, bacteraemia/bacteremia, gastroenteritis, incidence, prevalence, morbidity, mortality, case fatality, host/risk factor, vaccination, and prevention/control.
RECENT FINDINGS
Estimates of the global invasive nontyphoidal Salmonella disease burden have been recently updated; additional data from Africa, Asia, and Latin America are now available. New data bridge various knowledge gaps, particularly with respect to host risk factors and the geographical distribution of iNTS serovars. It has also been observed that Salmonella Typhimurium sequence type 313 is emergent in several African countries. Available data suggest that genetic variation in the sequence type 313 strain has led to increased pathogenicity and human host adaptation. A bivalent efficacious vaccine, targeting Salmonella serovars Typhimurium and Enteritidis, would significantly lower the disease burden in high-risk populations.
SUMMARY
The mobilization of surveillance networks, especially in Asia and Latin America, may provide missing data regarding the invasive nontyphoidal Salmonella disease burden and their corresponding antimicrobial susceptibility profiles. Efforts and resources should be directed toward invasive nontyphoidal Salmonella disease vaccine development.
Topics: Africa; Asia; Humans; Latin America; Salmonella Infections; Salmonella Vaccines; Salmonella enteritidis; Salmonella typhimurium
PubMed: 28731899
DOI: 10.1097/QCO.0000000000000398 -
FEMS Microbiology Reviews Sep 2021While conjugate vaccines against typhoid fever have recently been recommended by the World Health Organization for deployment, the lack of a vaccine against paratyphoid,... (Review)
Review
While conjugate vaccines against typhoid fever have recently been recommended by the World Health Organization for deployment, the lack of a vaccine against paratyphoid, multidrug resistance and chronic carriage all present challenges for the elimination of enteric fever. In the past decade, the development of in vitro and human challenge models has resulted in major advances in our understanding of enteric fever pathogenesis. In this review, we summarise these advances, outlining mechanisms of host restriction, intestinal invasion, interactions with innate immunity and chronic carriage, and discuss how this knowledge may progress future vaccines and antimicrobials.
Topics: Humans; Salmonella; Salmonella paratyphi A; Salmonella typhi; Typhoid Fever; Typhoid-Paratyphoid Vaccines
PubMed: 33733659
DOI: 10.1093/femsre/fuab014 -
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 -
Microbiology and Molecular Biology... Sep 2017subspecies includes several serovars infecting both humans and other animals and leading to typhoid fever or gastroenteritis. The high prevalence of associated... (Review)
Review
subspecies includes several serovars infecting both humans and other animals and leading to typhoid fever or gastroenteritis. The high prevalence of associated morbidity and mortality, together with an increased emergence of multidrug-resistant strains, is a current global health issue that has prompted the development of vaccination strategies that confer protection against most serovars. Currently available systemic vaccine approaches have major limitations, including a reduced effectiveness in young children and a lack of cross-protection among different strains. Having studied host-pathogen interactions, microbiologists and immunologists argue in favor of topical gastrointestinal administration for improvement in vaccine efficacy. Here, recent advances in this field are summarized, including mechanisms of bacterial uptake at the intestinal epithelium, the assessment of protective host immunity, and improved animal models that closely mimic infection in humans. The pros and cons of existing vaccines are presented, along with recent progress made with novel formulations. Finally, new candidate antigens and their relevance in the refined design of anti- vaccines are discussed, along with antigen vectorization strategies such as nanoparticles or secretory immunoglobulins, with a focus on potentiating mucosal vaccine efficacy.
Topics: Administration, Mucosal; Animals; Antibodies, Bacterial; Host-Pathogen Interactions; Humans; Immunity, Mucosal; Immunoglobulin A, Secretory; Immunoglobulin M; Intestinal Mucosa; Nanoparticles; Salmonella; Salmonella Infections; Salmonella Vaccines; Typhoid Fever; Vaccination
PubMed: 28615285
DOI: 10.1128/MMBR.00007-17 -
Expert Review of Vaccines Sep 2013Attenuated Salmonella vaccines can be administered orally to deliver recombinant antigens to mucosal surfaces inducing a protective immune response against a variety of... (Review)
Review
Attenuated Salmonella vaccines can be administered orally to deliver recombinant antigens to mucosal surfaces inducing a protective immune response against a variety of targeted pathogens. A number of exciting new approaches and technologies for attenuated Salmonella vaccines have been developed recently. However, a disconnect remains between results obtained with mice in preclinical studies and results obtained in human clinical trials. This is due to an incomplete understanding of Salmonella Typhi interactions with human hosts and inadequate animal models available for study. In this review, the authors describe recent progress in identifying important differences underlying S. Typhi-host interactions, the development of novel approaches to vaccine design and six recent clinical trials evaluating Salmonella-vectored vaccines.
Topics: Administration, Oral; Animals; Cell Surface Display Techniques; Clinical Trials as Topic; Disease Models, Animal; Drug Delivery Systems; Humans; Salmonella Vaccines; Salmonella typhi; Vaccination; Vaccines, Attenuated; Vaccines, Synthetic
PubMed: 24053397
DOI: 10.1586/14760584.2013.825454 -
Clinical and Vaccine Immunology : CVI Sep 2016Salmonellosis remains an important cause of human disease worldwide. While there are several licensed vaccines for Salmonella enterica serovar Typhi, these vaccines are... (Review)
Review
Salmonellosis remains an important cause of human disease worldwide. While there are several licensed vaccines for Salmonella enterica serovar Typhi, these vaccines are generally ineffective against other Salmonella serovars. Vaccines that target paratyphoid and nontyphoidal Salmonella serovars are very much in need. Preclinical evaluation of candidate vaccines is highly dependent on the availability of appropriate scientific tools, particularly animal models. Many different animal models exist for various Salmonella serovars, from whole-animal models to smaller models, such as those recently established in insects. Here, we discuss various mouse, rat, rabbit, calf, primate, and insect models for Salmonella infection, all of which have their place in research. However, choosing the right model is imperative in selecting the best vaccine candidates for further clinical testing. In this minireview, we summarize the various animal models that are used to assess salmonellosis, highlight some of the advantages and disadvantages of each, and discuss their value in vaccine development.
Topics: Animals; Disease Models, Animal; Drug Evaluation, Preclinical; Insecta; Mammals; Primates; Salmonella Infections; Salmonella Vaccines
PubMed: 27413068
DOI: 10.1128/CVI.00258-16