A Perspective on the Strategy for Advancing ETVAX®, An Anti-ETEC Diarrheal Disease Vaccine, into a Field Efficacy Trial in Gambian Children: Rationale, Challenges, Lessons Learned, and Future Directions DOI Creative Commons

M. Jahangir Hossain,

Ann‐Mari Svennerholm,

Nils Carlin

и другие.

Microorganisms, Год журнала: 2023, Номер 12(1), С. 90 - 90

Опубликована: Дек. 31, 2023

For the first time in over 20 years, an Enterotoxigenic Escherichia coli (ETEC) vaccine candidate, ETVAX®, has advanced into a phase 2b field efficacy trial for children 6–18 months of age low-income country. ETVAX® is inactivated whole cell that gone through series clinical trials to provide rationale design elements Phase trial. This now underway The Gambia and will be precursor upcoming pivotal 3 To reach this point, numerous findings were brought together define factors such as safe immunogenic doses children, possible benefit mucosal adjuvant, double mutant labile toxin (dmLT). Considering promising but still underexplored potential cells oral vaccination, we present perspective compiling key observations from past informed Gambian design. report update trial’s status explore future directions ETEC trials. Our aim not only on most candidate also offer insights beneficial development other much-needed whole-cell vaccines against enteric pathogens.

Язык: Английский

Regulation of oxidative stress in the intestine of piglets after enterotoxigenic Escherichia coli (ETEC) infection DOI

Shunshun Jin,

Haoxiang Xu,

Chengbo Yang

и другие.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Год журнала: 2024, Номер 1871(5), С. 119711 - 119711

Опубликована: Апрель 2, 2024

Язык: Английский

Процитировано

11
The role of vaccines in reducing antimicrobial resistance: A review of potential impact of vaccines on AMR and insights across 16 vaccines and pathogens DOI Creative Commons
Mateusz Hasso-Agopsowicz, Erin Sparrow,

Alexandra Meagan Cameron

и другие.

Vaccine, Год журнала: 2024, Номер 42(19), С. S1 - S8

Опубликована: Июнь 13, 2024

In 2019, an estimated 4.95 million deaths were linked to antimicrobial resistance (AMR). Vaccines can prevent many of these by averting both drug-sensitive and resistant infections, reducing antibiotic usage, lowering the likelihood developing genes. However, their role in mitigating AMR is currently underutilized. This article builds upon previous research that utilizes Vaccine Value Profiles—tools assess health, socioeconomic, societal impact pathogens—to inform vaccine development. We analyze effects 16 pathogens, covered Profiles, on AMR, explore how vaccines could reduce AMR. The also provides insights into development usage. are crucial lessening infectious diseases curbing To fully realize potential, must be more prominently featured overall strategy combat requires ongoing investment new implementation additional prevention control measures address this global threat effectively.

Язык: Английский

Процитировано

8
Targeting Enterotoxins: Advancing Vaccine Development for Enterotoxigenic Escherichia coli ETEC DOI Creative Commons

Josune Salvador-Erro,

Yadira Pastor, Carlos Gamazo

и другие.

Toxins, Год журнала: 2025, Номер 17(2), С. 71 - 71

Опубликована: Фев. 6, 2025

Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrheal disease worldwide, particularly in children low- and middle-income countries. Its ability to rapidly colonize the intestinal tract through diverse colonization factors toxins underpins its significant public health impact. Despite extensive research several vaccine candidates reaching clinical trials, no licensed exists for ETEC. This review explores temporal spatial coordination ETEC virulence factors, focusing on interplay between adherence mechanisms toxin production as critical targets therapeutic intervention. Advancements molecular biology host–pathogen interaction studies have uncovered species-specific variations cross-reactivity human animal strains. In particular, heat-labile (LT) heat-stable (ST) provided crucial insights into disruption. Additional exotoxins, such EAST-1 hemolysins, further highlight multifactorial nature pathogenicity. Innovative strategies, including multiepitope fusion antigens (MEFAs), mRNA-based approaches, glycoconjugates, aim enhance broad-spectrum immunity. Novel delivery methods, like intradermal immunization, show promise eliciting robust immune responses. Successful vaccination against will offer an effective affordable solution with potential greatly reduce mortality prevent stunting, representing highly impactful cost-efficient global challenge.

Язык: Английский

Процитировано

1
Special Issue on Enterotoxigenic Escherichia coli (ETEC) Vaccines: ETEC Infection and Vaccine-Mediated Immunity DOI Creative Commons
Frederick J. Cassels, Fakher Rahim,

A. Louis Bourgeois

и другие.

Microorganisms, Год журнала: 2024, Номер 12(6), С. 1087 - 1087

Опубликована: Май 27, 2024

Enterotoxigenic Escherichia coli (ETEC) is the most prevalent bacterial pathogen causing young children to suffer acute watery diarrhea in Low- and Middle-Income Countries (LMICs) [...]

Язык: Английский

Процитировано

4
Repeat modules and N-linked glycans define structure and antigenicity of a critical enterotoxigenic E. coli adhesin DOI Creative Commons
Zachary T. Berndsen, Marjahan Akhtar, Mahima Thapa

и другие.

PLoS Pathogens, Год журнала: 2024, Номер 20(9), С. e1012241 - e1012241

Опубликована: Сен. 16, 2024

Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions cases infectious diarrhea annually, predominantly in children from low-middle income regions. Notably, children, as well volunteers challenged with ETEC, diarrheal severity is significantly increased blood group A (bgA) individuals. EtpA, a secreted glycoprotein adhesin that functions lectin to promote critical interactions between ETEC and glycans on intestinal epithelia for effective bacterial adhesion toxin delivery. EtpA highly immunogenic resulting robust antibody responses following natural infection experimental challenge ETEC. To understand how directs ETEC-blood stimulates adaptive immunity, we mutated mapped its glycosylation by mass-spectrometry (MS), isolated polyclonal (pAbs) monoclonal antibodies (mAbs) vaccinated mice ETEC-infected volunteers, determined structures antibody-EtpA complexes cryo-electron microscopy. Both bgA mAbs inhibited EtpA-bgA adhesion, bound the C-terminal repeat domain highlighting this region crucial pathogen-host interaction. MS analysis uncovered extensive heterogeneous N-linked cryo-EM revealed directly engage these unique glycan containing epitopes. Finally, electron microscopy-based epitope mapping targeting numerous distinct epitopes N domains, suggesting vaccination generates against neutralizing decoy regions molecule. Collectively, anticipate data will inform our general understanding immunity relevant rational vaccine subunit design.

Язык: Английский

Процитировано

3
Efficacy of an Enterotoxigenic Escherichia coli (ETEC) Vaccine on the Incidence and Severity of Traveler’s Diarrhea (TD): Evaluation of Alternative Endpoints and a TD Severity Score DOI Creative Commons
Nicole Maier,

Shannon Grahek,

Jane L. Halpern

и другие.

Microorganisms, Год журнала: 2023, Номер 11(10), С. 2414 - 2414

Опубликована: Сен. 27, 2023

The efficacy of an Oral Whole Cell ETEC Vaccine (OEV) against Travelers' Diarrhea (TD) was reexamined using novel outcome and immunologic measures. More specifically, a recently developed disease severity score alternative clinical endpoints were evaluated as part initial validation effort to access the vaccine intervention for first time in travelers endemic area. A randomized, double-blind, placebo-controlled trial followed Guatemala or Mexico up 28 days after arrival country following vaccination (two doses two weeks apart) with vaccine. Fecal samples collected upon arrival, departure, during TD pathogen identification. Serum subset subjects determine IgA cholera toxin B subunit (CTB) antibody titers their country. vaccine's efficacy, utilizing other endpoints, including relationship between levels risk, assessed compared per-protocol primary endpoint. total 1435 completed 7-28 follow-up had available data. higher more severe (≥5 unformed stools/24 h) ETEC-attributable when accounting take (PE ≥ 50%;

Язык: Английский

Процитировано

3
Repeat modules and N-linked glycans define structure and antigenicity of a critical enterotoxigenicE. coli adhesin DOI Open Access
Zachary T. Berndsen, Marjahan Akhtar, Mahima Thapa

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 8, 2024

Enterotoxigenic

Язык: Английский

Процитировано

0
adhesiomeR: a tool for Escherichia coli adhesin classification and analysis DOI Creative Commons
Katarzyna Sidorczuk, Michał Burdukiewicz,

Klara Cerk

и другие.

BMC Genomics, Год журнала: 2024, Номер 25(1)

Опубликована: Июнь 17, 2024

Abstract Adhesins are crucial factors in the virulence of bacterial pathogens such as Escherichia coli . However, to date no resources have been dedicated detailed analysis E. adhesins. Here, we provide adhesiomeR software that enables characterization complete adhesin repertoire, termed adhesiome. AdhesiomeR incorporates most comprehensive database adhesins and facilitates an extensive We demonstrate achieves 98% accuracy when compared with experimental analyses. Based on 15,000 genomes, define novel adhesiome profiles clusters, providing a nomenclature for unified comparison adhesiomes.

Язык: Английский

Процитировано

0
A Perspective on the Strategy for Advancing ETVAX®, An Anti-ETEC Diarrheal Disease Vaccine, into a Field Efficacy Trial in Gambian Children: Rationale, Challenges, Lessons Learned, and Future Directions DOI Creative Commons

M. Jahangir Hossain,

Ann‐Mari Svennerholm,

Nils Carlin

и другие.

Microorganisms, Год журнала: 2023, Номер 12(1), С. 90 - 90

Опубликована: Дек. 31, 2023

For the first time in over 20 years, an Enterotoxigenic Escherichia coli (ETEC) vaccine candidate, ETVAX®, has advanced into a phase 2b field efficacy trial for children 6–18 months of age low-income country. ETVAX® is inactivated whole cell that gone through series clinical trials to provide rationale design elements Phase trial. This now underway The Gambia and will be precursor upcoming pivotal 3 To reach this point, numerous findings were brought together define factors such as safe immunogenic doses children, possible benefit mucosal adjuvant, double mutant labile toxin (dmLT). Considering promising but still underexplored potential cells oral vaccination, we present perspective compiling key observations from past informed Gambian design. report update trial’s status explore future directions ETEC trials. Our aim not only on most candidate also offer insights beneficial development other much-needed whole-cell vaccines against enteric pathogens.

Язык: Английский

Процитировано

1