Evidence map›Paper›PMID 37400283›Full record

ArticleVaccine2023

Development of Shigella conjugate vaccines targeting Shigella flexneri 2a and S. flexneri 3a using a simple platform-approach conjugation by squaric acid chemistry.

Meagan Kelly, Anjali Mandlik, Richelle C Charles, Smriti Verma, Stephen B Calderwood, Daniel T Leung, Rajib Biswas, Kamrul Islam, Mohammad Kamruzzaman, Fahima Chowdhury and 10 more

Open access · hybridAbstract read
In one paragraph

Article in Vaccine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.7field-weighted citation impact, top 11% of its field
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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Development of a NovelVaccines · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. International journal of molecular sciences · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 7 institutions in 2 countries.

Meagan KellyDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
Anjali MandlikDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
Richelle C CharlesDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Smriti VermaDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
Stephen B CalderwoodDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
Daniel T LeungDivision of Infectious Diseases, University of Utah, Salt Lake City, Utah, USA.
Rajib Biswasicddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh.
Kamrul Islamicddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh.
Mohammad Kamruzzamanicddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh.
Fahima Chowdhuryicddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh.
Farhana Khanamicddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh.
Willie F VannCenter for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Ashraful Islam Khanicddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh.
Taufiqur Rahman Bhuiyanicddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh.
Firdausi Qadriicddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh.
Anthony R VorthermsDepartment of Diarrheal Disease Research, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Bethesda, MD, USA.
Robert KaminskiDepartment of Diarrheal Disease Research, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Bethesda, MD, USA.
Pavol KováčNIDDK, LBC, National Institutes of Health, Bethesda, MD, USA.
Peng XuNIDDK, LBC, National Institutes of Health, Bethesda, MD, USA.
Edward T RyanDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: etryan@mgh.harvard.edu.
International Centre for Diarrhoeal Disease Research · BDHarvard University · USMassachusetts General Hospital · USNational Institutes of Health · USWalter Reed Army Institute of Research · USCenter for Biologics Evaluation and Research · USUniversity of Utah · US

Funding

Training program in vaccine development and public healthD43TW005572 · FIC · MASSACHUSETTS GENERAL HOSPITAL · PI QADRI, FIRDAUSI, RYAN, EDWARD T. · 2000 to 2025
$5.4M
Functional profiling of OSP-specific and other antibodies during shigella infectionR01AI155414 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Edward T. Ryan · 2020 to 2026
$5.3M
O-Specific Polysaccharide Responses and CholeraR37AI106878 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Edward T. Ryan · 2020 to 2026
$5.1M
Shigella Conjugate Vaccine (SCV4) Development, Characterization, and Pre-clinical EvaluationR01AI177075 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Edward T. Ryan · 2023 to 2026
$4.3M
O-Specific Polysaccharide Responses and CholeraR01AI106878 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI RYAN, EDWARD T. · 2014 to 2018
$3.7M
O-Specific Polysaccharide Responses and CholeraR56AI106878 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI RYAN, EDWARD T. · 2013 to 2020
$843k
Humoral and adaptive immune responses study in Vibrio cholerae infectionK43TW010362 · FIC · INTERNATIONAL CTR/DIARRHOEAL DIS RES · PI BHUIYAN, MD TAUFIQUR RAHMAN · 2016 to 2020
$359k
FIC NIH HHS D43 TW005572FIC NIH HHS K43 TW010362NIAID NIH HHS R01 AI106878NIAID NIH HHS R01 AI155414NIAID NIH HHS R01 AI177075NIAID NIH HHS R37 AI106878NIAID NIH HHS R56 AI106878
6 · The paper itself

Abstract

There is a need for vaccines effective against shigella infection in young children in resource-limited areas. Protective immunity against shigella infection targets the O-specific polysaccharide (OSP) component of lipopolysaccharide. Inducing immune responses to polysaccharides in young children can be problematic, but high level and durable responses can be induced by presenting polysaccharides conjugated to carrier proteins. An effective shigella vaccine will need to be multivalent, targeting the most common global species and serotypes such as Shigella flexneri 2a, S. flexneri 3a, S. flexneri 6, and S. sonnei. Here we report the development of shigella conjugate vaccines (SCV) targeting S. flexneri 2a (SCV-Sf2a) and 3a (SCV-Sf3a) using squaric acid chemistry to result in single point sun-burst type display of OSP from carrier protein rTTHc, a 52 kDa recombinant protein fragment of the heavy chain of tetanus toxoid. We confirmed structure and demonstrated that these conjugates were recognized by serotype-specific monoclonal antibodies and convalescent sera of humans recovering from shigellosis in Bangladesh, suggesting correct immunological display of OSP. We vaccinated mice and found induction of serotype-specific OSP and LPS IgG responses, as well as rTTHc-specific IgG responses. Vaccination induced serotype-specific bactericidal antibody responses against S. flexneri, and vaccinated animals were protected against keratoconjunctivitis (Sereny test) and intraperitoneal challenge with virulent S. flexneri 2a and 3a, respectively. Our results support further development of this platform conjugation technology in the development of shigella conjugate vaccines for use in resource-limited settings.

Indexed as

Dysentery, BacillaryShigellaShigella VaccinesAnimalsAntibodies, BacterialChildChild, PreschoolCyclobutanesHumansImmunoglobulin GLipopolysaccharidesMiceO AntigensShigella flexneriVaccines, ConjugateAntibodies, BacterialCyclobutanesImmunoglobulin GLipopolysaccharidesO AntigensShigella Vaccinessquaric acidVaccines, ConjugateConjugateImmunityS. flexneri 2aS. flexneri 3aShigellaShigellosisSquaric acidVaccine

Identifiers

PMID37400283
PMCPMC10529421
OpenAlexW4382794848

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.