Evidence map›Paper›PMID 39116906›Full record

ArticleThe Lancet. Microbe2024

Determinants of immune responses predictive of protection against shigellosis in an endemic zone: a systems analysis of antibody profiles and function.

Biana Bernshtein, Meagan Kelly, Deniz Cizmeci, Julia A Zhiteneva, Ryan Macvicar, Mohammad Kamruzzaman, Taufiqur R Bhuiyan, Fahima Chowdhury, Ashraful Islam Khan, Firdausi Qadri and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Microbe, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. mBio · 2025
    Article
  6. Review
  7. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Biana BernshteinRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA, USA. Electronic address: bbernshtein@mgh.harvard.edu.
Meagan KellyDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
Deniz CizmeciRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA, USA.
Julia A ZhitenevaRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA, USA.
Ryan MacvicarRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA, USA.
Mohammad KamruzzamanInternational Centre for Diarrheal Disease Research Bangladesh (icddr,b), Dhaka, Bangladesh; Department of Biochemistry and Molecular Biology, Mawlana Bhashani Science and Technology University, Tangail, Bangladesh.
Taufiqur R BhuiyanInternational Centre for Diarrheal Disease Research Bangladesh (icddr,b), Dhaka, Bangladesh.
Fahima ChowdhuryInternational Centre for Diarrheal Disease Research Bangladesh (icddr,b), Dhaka, Bangladesh.
Ashraful Islam KhanInternational Centre for Diarrheal Disease Research Bangladesh (icddr,b), Dhaka, Bangladesh.
Firdausi QadriInternational Centre for Diarrheal Disease Research Bangladesh (icddr,b), Dhaka, Bangladesh.
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.
Peng XuNational Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Bioorganic Chemistry, National Institutes of Health, Bethesda, MD, USA.
Pavol KováčNational Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Bioorganic Chemistry, National Institutes of Health, Bethesda, MD, USA.
Kristen A ClarksonDepartment of Diarrheal Disease Research, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Robert W KaminskiDepartment of Diarrheal Disease Research, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Latham BioPharm Group, Cambridge, MA, USA.
Galit AlterRagon Institute of Mass General, MIT, and Harvard, Cambridge, MA, 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.

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
Shigella Conjugate Vaccine (SCV4) Development, Characterization, and Pre-clinical EvaluationR01AI177075 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Edward T. Ryan · 2023 to 2026
$4.3M
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 AI155414NIAID NIH HHS R01 AI177075
6 · The paper itself

Abstract

backgroundShigella is the third leading global cause of moderate or severe diarrhoea among children younger than 5 years globally, and is the leading cause in children aged 24-59 months. The mechanism of protection against Shigella infection and disease in endemic areas is uncertain. We aimed to compare the Shigella-specific antibody responses in individuals living in Shigella-endemic and non-endemic areas, and to identify correlates of protection in a Shigella-endemic location.

methodsWe applied a systems approach to retrospectively analyse serological responses to Shigella across endemic and non-endemic populations. We profiled serum samples collected from 44 individuals from the USA without previous exposure to Shigella and who were experimentally challenged with Shigella sonnei (non-endemic setting), and serum samples collected from 55 Peruvian army recruits (endemic setting). In the endemic setting, a subset of 37 samples collected from individuals infected with culture-confirmed Shigella flexneri 2a were divided into two groups: susceptible, which included individuals infected within 90 days of entering the camp (n=29); or resistant, which included individuals infected later than 90 days after entering the camp (n=8). We analysed Shigella-specific antibody isotype, subclass, and Fc receptor binding profiles across IpaB, IpaC, IpaD, and lipopolysaccharide from S flexneri 2a, 3a, and 6, and S sonnei, and O-specific polysaccharide (OSP) from S flexneri 2a and 3a and S sonnei. We also evaluated antibody-mediated complement deposition and innate immune cell activation. The main outcome of interest was the detection of antibody markers and functionality associated with protection against shigellosis in a high-burden endemic setting.

findingsAdults with endemic exposure to Shigella possessed broad and functional antibody responses across polysaccharide, glycolipid, and protein antigens compared with individuals from non-endemic regions. In a setting with high Shigella burden, elevated levels of OSP-specific Fcα receptor (FcαR) binding antibodies were associated with resistance to shigellosis, whereas total OSP-specific IgA was not, suggesting a potentially unique functionality. OSP-specific FcαR binding IgA found in resistant individuals activated bactericidal neutrophil functions including phagocytosis, degranulation, and production of reactive oxygen species. Moreover, IgA depletion from resistant serum significantly reduced binding of OSP-specific antibodies to FcαR and antibody-mediated activation of neutrophils and monocytes.

interpretationOur findings suggest that OSP-specific functional IgA responses contribute to protective immunity against Shigella infection in a high-burden setting. These findings will assist in the development and evaluation of Shigella vaccines.

fundingUS National Institutes of Health.

Indexed as

Antibodies, BacterialDysentery, BacillaryEndemic DiseasesShigella sonneiAdolescentAdultFemaleHumansMalePeruRetrospective StudiesShigella flexneriUnited StatesYoung AdultAntibodies, Bacterial

Identifiers

PMID39116906
PMCPMC11488819

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LicenceCC BY-NC-ND
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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.