Impact of an intranasal L-DBF vaccine on the gut microbiota in young and elderly mice DOI Creative Commons
Ti Lu, Aaron C. Ericsson,

Zackary K. Dietz

et al.

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: Nov. 9, 2024

spp. cause bacillary dysentery (shigellosis) with high morbidity and mortality in low- middle-income countries. Infection occurs through the fecal-oral route can be devastating for vulnerable populations, including infants elderly. These bacteria invade host cells using a type III secretion system (T3SS). No licensed vaccine yet exists shigellosis, but we have generated recombinant fusion protein, L-DBF, combining T3SS needle tip protein (IpaD), translocator (IpaB), LTA1 subunit of enterotoxigenic

Language: Английский

A broad spectrum Shigella vaccine based on VirG53–353 multiepitope region produced in a cell-free system DOI Creative Commons
Girmay Desalegn, Charlotte H. Abrahamson, K. Ross Turbyfill

et al.

npj Vaccines, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 13, 2025

Dysentery caused by Shigella species remains a major health threat to children in low- and middle-income countries. There is no vaccine available. The most advanced candidates, i.e., O-polysaccharide (OPS)-based conjugates, have limited coverage—only against the immunizing serotype. Vaccines based on conserved proteins are sought for their simplicity capacity prevent disease multiple serotypes. We previously reported broad protective of VirGα, surface-exposed domain virulence factor. Seeking refine antigenic target achieve scalable manufacturing compatible with Good Manufacturing Practices, we mapped linear B-cell epitopes spanning entire VirG protein sequence probing immune reactivity 10-mer peptides (overlapping 4–8 aa) sera from Shigella-infected rhesus monkeys. VirG53–353 subregion passenger α-domain demonstrated highest strongest immunoreactivity. was produced efficiently at large scale (>150 mg/L) using cell-free synthesis. When administered mice intramuscularly, elicited robust antibody responses conferred high levels protection three prevalent serotypes (S. flexneri 2a, 3a, S. sonnei). evoked production Th2-type cytokines spleen cells vaccinated mice. A new universal meets World Health Organization's preferred product specifications. antigen refinement improvement described here will facilitate first-in-human studies.

Language: Английский

Citations

0
Development of a Novel mRNA Vaccine Against Shigella Pathotypes Causing Widespread Shigellosis Endemic: An In-Silico Immunoinformatic Approach DOI Creative Commons
Abdur Razzak, Otun Saha,

Khandokar Fahmida Sultana

et al.

Bioinformatics and Biology Insights, Journal Year: 2025, Volume and Issue: 19

Published: March 1, 2025

Shigellosis remains a major global health concern, particularly in regions with poor sanitation and limited access to clean water. This study used immunoinformatics reverse vaccinology design potential mRNA vaccine targeting Shigella pathotypes out of 4071 proteins from sonnei str. Ss046, 4 key antigenic candidates were identified: putative outer membrane protein (Q3YZL0), PapC-like porin (Q3YZM5), fimbrial-like (Q3Z3I2), lipopolysaccharide (LPS)-assembly LptD (Q3Z5V5), ensuring broad pathotype coverage. A multitope was designed incorporating cytotoxic T lymphocyte, helper B-cell epitopes, linked suitable linkers adjuvants enhance immunogenicity. Computational analyses predicted vaccine's favorable antigenicity, solubility, stability, while molecular docking dynamic simulations demonstrated strong binding affinity stability Toll-like receptor (TLR-4), indicating for robust immune activation. Immune humoral cellular responses, characterized by significant cytokine production long-term memory. Structural evaluations the complex, including radius gyration, root mean square deviation, fluctuation, solvent accessibility, confirmed structural integrity, under physiological conditions. research contributes ongoing effort alleviate burden infections, providing foundation future wet laboratory investigations aimed at development.

Language: Английский

Citations

0
Spatial visualization provides insight into immune modulation by an L-DBF vaccine formulation against Shigella DOI Creative Commons
Ti Lu, Skyler T. Kramer, Mary K. York

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 23, 2025

Shigellosis remains a global public health problem, especially in regions with poor sanitation measures. Our prior work has demonstrated the protective efficacy of three-dose regimen L-DBF, recombinant fusion IpaD and IpaB from Shigella flexneri LTA1 moiety enterotoxigenic E. coli labile toxin. Here, we investigate how two-dose (one prime one booster) formulated an oil-in-water emulsion called ME, modulates immune responses lung using spatial transcriptomics approach. findings show significant changes landscape following vaccination, including increased expression B cell markers, antigen presentation genes, T cell-associated markers. analysis also revealed reprogramming fibroblasts cardiomyocytes, showing that are shifted extracellular matrix production to modulation, while cardiomyocytes enhanced signaling for recruitment vascular stability. The communication between alveolar type 2 (AT2) cells increased, reflecting coordinated support readiness maintaining tissue integrity. These underscore potential L-DBF/ME vaccination enhance both humoral cellular immunity, as well reshape architecture enhancing readiness, thereby offering promising approach effective protection against infections.

Language: Английский

Citations

0
Vaccination with a Protective Ipa Protein-Containing Nanoemulsion Differentially Alters the Transcriptomic Profiles of Young and Elderly Mice following Shigella Infection DOI Creative Commons
Ti Lu, Murugesan Raju, Debaki R. Howlader

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(6), P. 618 - 618

Published: June 4, 2024

Shigella spp. are responsible for bacillary dysentery or shigellosis transmitted via the fecal–oral route, causing significant morbidity and mortality, especially among vulnerable populations. There currently no licensed vaccines. use a type III secretion system (T3SS) to invade host cells. We have shown that L-DBF, recombinant fusion of T3SS needle tip (IpaD) translocator (IpaB) proteins with LTA1 subunit enterotoxigenic E. coli labile toxin, is broadly protective against challenge in mouse lethal pulmonary model. Here, we assessed effect LDBF, formulated unique TLR4 agonist called BECC470 an oil-in-water emulsion (ME), on murine immune response high-risk population (young elderly) challenge. Dual RNA Sequencing captured transcriptome during infection vaccinated unvaccinated mice. Both age groups were protected by L-DBF formulation, while younger mice exhibited more adaptive gene patterns. This preliminary study provides step toward identifying expression patterns regulatory pathways Shigella. Furthermore, this measure challenges need be addressed when immunizing aging population.

Language: Английский

Citations

2
Bacteria carrying mobile colistin resistance genes and their control measures, an updated review DOI
Qi Zhang

Archives of Microbiology, Journal Year: 2024, Volume and Issue: 206(12)

Published: Nov. 8, 2024

Language: Английский

Citations

1
Mechanisms of resistance and decreased susceptibility to azithromycin in Shigella DOI
Zohreh Ghalavand, Parisa Behruznia, Mansoor Kodori

et al.

Gene Reports, Journal Year: 2024, Volume and Issue: 37, P. 102011 - 102011

Published: Aug. 10, 2024

Language: Английский

Citations

0
Limited O-specific polysaccharide (OSP)-specific functional antibody responses in young children with Shigella infection in Bangladesh DOI
Biana Bernshtein,

Julia A. Zhiteneva,

Jeshina Janardhanan

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 8, 2024

Shigellosis is the second leading cause of diarrheal death in children younger than five years age globally. At present, there no broadly licensed vaccine against shigella infection. Previous candidates have failed at providing protection for young endemic settings. Improved understanding correlates Shigella infection and severe shigellosis living settings needed. Here, we applied a functional antibody profiling approach to define Shigella-specific responses versus older individuals with culture-confirmed Bangladesh, area. We analyzed isotypes, FcR binding antibody-mediated innate immune cell activation longitudinal serum samples collected clinical presentation up 1 year later. found that higher initial O-specific polysaccharide (OSP)-specific protein-specific IgG FcγR levels correlated less disease regardless patient age, but under 5 developed prominent class switched, FcR-binding, durable response both OSP protein antigens individuals. Focusing on largest cohort,

Language: Английский

Citations

0
Impact of an intranasal L-DBF vaccine on the gut microbiota in young and elderly mice DOI Creative Commons
Ti Lu, Aaron C. Ericsson,

Zackary K. Dietz

et al.

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: Nov. 9, 2024

spp. cause bacillary dysentery (shigellosis) with high morbidity and mortality in low- middle-income countries. Infection occurs through the fecal-oral route can be devastating for vulnerable populations, including infants elderly. These bacteria invade host cells using a type III secretion system (T3SS). No licensed vaccine yet exists shigellosis, but we have generated recombinant fusion protein, L-DBF, combining T3SS needle tip protein (IpaD), translocator (IpaB), LTA1 subunit of enterotoxigenic

Language: Английский

Citations

0