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Frontiers in Immunology 2023, a Gram-negative pathogen, has over 2500 serovars that infect a wide range of hosts. In humans, causes typhoid or gastroenteritis and is a major public health concern....
, a Gram-negative pathogen, has over 2500 serovars that infect a wide range of hosts. In humans, causes typhoid or gastroenteritis and is a major public health concern. In this study, SseB (the tip protein of the pathogenicity island 2 type III secretion system) was fused with the LTA1 subunit of labile-toxin from enterotoxigenic to make the self-adjuvanting antigen L-SseB. Two unique nanoparticle formulations were developed to allow multimeric presentation of L-SseB. Mice were vaccinated with these formulations and protective efficacy determined challenging the mice with serovars. The polysaccharide (chitosan) formulation was found to elicit better protection when compared to the squalene nanoemulsion. When the polysaccharide formulation was used to vaccinate rabbits, protection from challenge was elicited. In summary, L-SseB in a particulate polysaccharide formulation appears to be an attractive candidate vaccine capable of broad protection against
Topics: Humans; Mice; Animals; Rabbits; Escherichia coli; Salmonella Infections; Typhoid Fever; Salmonella enterica; Typhoid-Paratyphoid Vaccines
PubMed: 37457702
DOI: 10.3389/fimmu.2023.1208848 -
Human Vaccines & Immunotherapeutics Aug 2023Vaccination stands as one of the most important scientific discoveries and public health achievements in the fight against diseases. For over a century, millions of... (Review)
Review
Vaccination stands as one of the most important scientific discoveries and public health achievements in the fight against diseases. For over a century, millions of early childhood deaths have been averted through routine immunizations. However, to prevent the morbidity and mortality associated with vaccine-preventable diseases and their complications and optimize the control of vaccine-preventable diseases in communities, high uptake rates must be achieved. Mass immunization campaigns (MICs) have globally been used to introduce new vaccines for major infectious diseases and improve coverage of routine vaccines through catch-up campaigns. Malawi recently undertook such a campaign to introduce a highly efficacious typhoid conjugate vaccine and provides a catch-up to measles, rubella, and polio. Such campaigns are associated with multiple benefits. However, the MICs are associated with multiple challenges to be successfully administered. In this review, we highlight recent MIC, vaccine coverage, and potential challenges and benefits and offer recommendation for future preventive campaigns.
Topics: Child, Preschool; Humans; Typhoid Fever; Malawi; Vaccine-Preventable Diseases; Vaccination; Immunization; Rubella; Measles; Typhoid-Paratyphoid Vaccines; Poliomyelitis
PubMed: 37431661
DOI: 10.1080/21645515.2023.2233397 -
The Journal of Clinical Investigation Aug 2023BACKGROUNDTyphoid fever is caused by the Gram-negative bacterium Salmonella enterica serovar Typhi and poses a substantial public health burden worldwide. Vaccines have... (Clinical Trial)
Clinical Trial
BACKGROUNDTyphoid fever is caused by the Gram-negative bacterium Salmonella enterica serovar Typhi and poses a substantial public health burden worldwide. Vaccines have been developed based on the surface Vi-capsular polysaccharide of S. Typhi; these include a plain-polysaccharide-based vaccine, ViPS, and a glycoconjugate vaccine, ViTT. To understand immune responses to these vaccines and their vaccine-induced immunological protection, molecular signatures were analyzed using bioinformatic approaches.METHODSBulk RNA-Seq data were generated from blood samples obtained from adult human volunteers enrolled in a vaccine trial, who were then challenged with S. Typhi in a controlled human infection model (CHIM). These data were used to conduct differential gene expression analyses, gene set and modular analyses, B cell repertoire analyses, and time-course analyses at various post-vaccination and post-challenge time points between participants receiving ViTT, ViPS, or a control meningococcal vaccine.RESULTSTranscriptomic responses revealed strong differential molecular signatures between the 2 typhoid vaccines, mostly driven by the upregulation in humoral immune signatures, including selective usage of immunoglobulin heavy chain variable region (IGHV) genes and more polarized clonal expansions. We describe several molecular correlates of protection against S. Typhi infection, including clusters of B cell receptor (BCR) clonotypes associated with protection, with known binders of Vi-polysaccharide among these.CONCLUSIONThe study reports a series of contemporary analyses that reveal the transcriptomic signatures after vaccination and infectious challenge, while identifying molecular correlates of protection that may inform future vaccine design and assessment.TRIAL REGISTRATIONClinicalTrials.gov NCT02324751.
Topics: Adult; Humans; Polysaccharides, Bacterial; Receptors, Antigen, B-Cell; Salmonella typhi; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccination
PubMed: 37402153
DOI: 10.1172/JCI169676 -
Human Vaccines & Immunotherapeutics Dec 2023Typhoid remains one of the major serious health concerns for children in developing countries. With extremely drug-resistant cases emerging, preventative measures like... (Randomized Controlled Trial)
Randomized Controlled Trial
A randomized, observer-blind, controlled phase III clinical trial assessing safety and immunological non-inferiority of Vi-diphtheria toxoid versus Vi-tetanus toxoid typhoid conjugate vaccine in healthy volunteers in eastern Nepal.
Typhoid remains one of the major serious health concerns for children in developing countries. With extremely drug-resistant cases emerging, preventative measures like sanitation and vaccination, including typhoid conjugate vaccines (TCV) remain the mainstay in its prevention and control. Different types of TCVs are being developed to meet the global demand. This report outlines the results from a study done to assess the immunogenicity and safety of Vi-Diphtheria toxoid (Vi-DT) TCV in Nepal. The study was a randomized, active-controlled, immunological non-inferiority and safety study. Eligible participants from Sunsari and Morang districts of eastern Nepal were randomized into 4 study groups (A-D) within 3 age strata (6 months to <2 years, 2 to <18 years, and 18 to 45 years). Groups A to C received a single dose (25 μg) of Vi-DT test vaccine from any of the 3 lots, while group D received the comparator, Typbar-TCV®, Vi-tetanus toxoid (Vi-TT) vaccine (25 μg) in 1:1:1:1 ratio and evaluated at 4 weeks postvaccination with 6 months follow-up. Amongst 400 randomized participants, anti-Vi-IgG seroconversion rates for all age strata in Vi-DT pooled groups (A+B+C) were 100.00% (97.5% CI 98.34-100.00) vs 98.99% (97.5% CI 93.99-99.85) in Vi-TT group (D) at 4 weeks. Comparable safety events were reported between the groups. Three serious adverse events (1 in Vi-DT; 2 in Vi-TT group) were reported during the 6 months follow-up, none being related to the investigational product. Thus, Vi-DT vaccine is safe, immunogenic, and immunologically non-inferior to Vi-TT when analyzed at 4 weeks postvaccination.
Topics: Child; Humans; Infant; Child, Preschool; Typhoid Fever; Vaccines, Conjugate; Tetanus Toxoid; Nepal; Healthy Volunteers; Diphtheria Toxoid; Typhoid-Paratyphoid Vaccines; Antibodies, Bacterial
PubMed: 37128723
DOI: 10.1080/21645515.2023.2203634 -
Clinical Infectious Diseases : An... Jul 2023The World Health Organization recommends vaccines for prevention and control of typhoid fever, especially where antimicrobial-resistant typhoid circulates. In 2018, the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The World Health Organization recommends vaccines for prevention and control of typhoid fever, especially where antimicrobial-resistant typhoid circulates. In 2018, the Navi Mumbai Municipal Corporation (NMMC) implemented a typhoid conjugate vaccine (TCV) campaign. The campaign targeted all children aged 9 months through 14 years within NMMC boundaries (approximately 320 000 children) over 2 vaccination phases. The phase 1 campaign occurred from 14 July 2018 through 25 August 2018 (71% coverage, approximately 113 420 children). We evaluated the phase 1 campaign's programmatic effectiveness in reducing typhoid cases at the community level.
METHODS
We established prospective, blood culture-based surveillance at 6 hospitals in Navi Mumbai and offered blood cultures to children who presented with fever ≥3 days. We used a cluster-randomized (by administrative boundary) test-negative design to estimate the effectiveness of the vaccination campaign on pediatric typhoid cases. We matched test-positive, culture-confirmed typhoid cases with up to 3 test-negative, culture-negative controls by age and date of blood culture and assessed community vaccine campaign phase as an exposure using conditional logistic regression.
RESULTS
Between 1 September 2018 and 31 March 2021, we identified 81 typhoid cases and matched these with 238 controls. Cases were 0.44 times as likely to live in vaccine campaign communities (programmatic effectiveness, 56%; 95% confidence interval [CI], 25% to 74%; P = .002). Cases aged ≥5 years were 0.37 times as likely (95% CI, .19 to .70; P = .002) and cases during the first year of surveillance were 0.30 times as likely (95% CI, .14 to .64; P = .002) to live in vaccine campaign communities.
CONCLUSIONS
Our findings support the use of TCV mass vaccination campaigns as effective population-based tools to combat typhoid fever.
Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Incidence; India; Prospective Studies; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccines, Attenuated; Vaccines, Conjugate
PubMed: 36947143
DOI: 10.1093/cid/ciad132 -
Clinical Infectious Diseases : An... Jul 2023
Topics: Child; Humans; Typhoid Fever; Vaccines, Conjugate; Typhoid-Paratyphoid Vaccines; Public Sector; India
PubMed: 36947122
DOI: 10.1093/cid/ciad134 -
Pediatrics and Neonatology Sep 2023Typhoid fever is a serious concern precisely in developing nations. Still investigators are exploring a better conjugate partner for Vi-polysaccharide to develop a more...
Typhoid fever is a serious concern precisely in developing nations. Still investigators are exploring a better conjugate partner for Vi-polysaccharide to develop a more effective vaccine for typhoid fever. Here, we cloned and expressed S. Typhi outer membrane protein A (OmpA). The conjugation of Vi-polysaccharide with OmpA was carried out by the carbodiimide (EDAC) method employing ADH as a linker. Total Ig and IgG generated against OmpA, and Vi polysaccharide was quantified by ELISA. Vi polysaccharide alone induced very low levels of Vi polysaccharide antibody. Vi-OmpA conjugate (Vi-conjugate) elicited a robust immune response compared to Vi polysaccharide alone and showed booster response. Further, IgG was only evoked by Vi-OmpA conjugate, not with Vi polysaccharide alone. OmpA antibody induction in both the Vi-OmpA conjugate and OmpA were similar level. Taken together, we show that OmpA as a carrier protein conjugated to Vi polysaccharide is immunogenic. We predict OmpA antibodies will contribute protection along with antibodies generated by Vi-polysaccharide. Past and current literature supports that OmpA is highly conserved protein not only among Salmonellae but entire Enterobacteriacea family with 96-100% identity.
Topics: Animals; Mice; Typhoid Fever; Salmonella typhi; Polysaccharides, Bacterial; Typhoid-Paratyphoid Vaccines; Antibodies, Bacterial; Immunoglobulin G; Immunity; Vaccines, Conjugate
PubMed: 36868948
DOI: 10.1016/j.pedneo.2022.12.011