Evidence map›Paper›PMID 39946867›Full record

ArticleVaccine2025

BECC-engineered live-attenuated Shigella vaccine candidates display reduced endotoxicity with robust immunogenicity in mice.

Matthew E Sherman, Jane Michalski, Sayan Das, Hyojik Yang, Lakshmi Chandrasekaran, Timothy R O'Meara, David J Dowling, Ofer Levy, Shoshana Barnoy, Malabi Venkatesan and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Vaccine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Characterization of the role of putativeJournal of bacteriology · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Matthew E ShermanUniversity of Maryland-Baltimore, Department of Microbial Pathogenesis, Baltimore, MD 21201, USA.
Jane MichalskiUniversity of Maryland-Baltimore, Department of Microbial Pathogenesis, Baltimore, MD 21201, USA; University of Maryland School of Medicine, Institute for Genome Sciences, Baltimore, MD 21201, USA.
Sayan DasUniversity of Maryland-Baltimore, Department of Microbial Pathogenesis, Baltimore, MD 21201, USA.
Hyojik YangUniversity of Maryland-Baltimore, Department of Microbial Pathogenesis, Baltimore, MD 21201, USA.
Lakshmi ChandrasekaranWalter Reed Army Institute of Research, Department of Diarrheal Disease Research, Bacterial Disease Branch, Silver Spring, MD 20910, USA.
Timothy R O'MearaPrecision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
David J DowlingPrecision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Ofer LevyPrecision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT & Harvard, Cambridge, MA 02142, USA.
Shoshana BarnoyWalter Reed Army Institute of Research, Department of Diarrheal Disease Research, Bacterial Disease Branch, Silver Spring, MD 20910, USA.
Malabi VenkatesanWalter Reed Army Institute of Research, Department of Diarrheal Disease Research, Bacterial Disease Branch, Silver Spring, MD 20910, USA.
Robert K ErnstUniversity of Maryland-Baltimore, Department of Microbial Pathogenesis, Baltimore, MD 21201, USA. Electronic address: rkernst@umaryland.edu.

Funding

Technology CoreU19AI110820 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI WHITE, OWEN R · 2014 to 2023
$36.5M
NIAID NIH HHS U19 AI110820
6 · The paper itself

Abstract

Shigella spp. infection contributes significantly to the global disease burden, primarily affecting young children in developing countries. Currently, there are no FDA-approved vaccines against Shigella, and the prevalence of antibiotic resistance is increasing, making therapeutic options limited. Live-attenuated vaccine strains WRSs2 (S. sonnei) and WRSf2G12 (S. flexneri 2a) are highly immunogenic, making them promising vaccine candidates, but possess an inflammatory lipid A structure on their lipopolysaccharide (LPS; also known as endotoxin). Here, we utilized bacterial enzymatic combinatorial chemistry (BECC) to ectopically express lipid A modifying enzymes in WRSs2 and WRSf2G12, as well as their respective wild-type strains, generating targeted lipid A modifications across the Shigella backgrounds. Dephosphorylation of lipid A, rather than deacylation, reduced LPS-induced TLR4 signaling in vitro and dampened endotoxic effects in vivo. These BECC-modified vaccine strains retained the phenotypic traits of their parental strains, such as invasion of epithelial cells and immunogenicity in mice without adverse endotoxicity. Overall, our observations suggest that BECC-engineered live attenuated vaccines are a promising approach to safe and effective Shigella vaccines.

Indexed as

Dysentery, BacillaryImmunogenicity, VaccineShigella VaccinesAnimalsFemaleHumansLipid ALipopolysaccharidesMiceMice, Inbred BALB CShigella flexneriShigella sonneiToll-Like Receptor 4Vaccines, AttenuatedLipid ALipopolysaccharidesShigella VaccinesToll-Like Receptor 4Vaccines, AttenuatedBECCEndotoxicityLipid ALive-attenuated vaccineLPSShigella

Identifiers

PMID39946867
PMCPMC13659338

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.