Evidence map›Paper›PMID 30985006›Full record

ArticleClinical and experimental immunology2019

Use of bioengineered human commensal gut bacteria-derived microvesicles for mucosal plague vaccine delivery and immunization.

A L Carvalho, A Miquel-Clopés, U Wegmann, E Jones, R Stentz, A Telatin, N J Walker, W A Butcher, P J Brown, S Holmes and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Clinical and experimental immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

24 citing papers in PubMed, 42 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Delivery ofmSphere · 2024
    Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Biological Nanoparticles in Vaccine Development.Frontiers in bioengineering and biotechnology · 2022
    Review
  13. TheFrontiers in microbiology · 2022
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Plague vaccines: new developments in an ongoing search.Applied microbiology and biotechnology · 2021
    Review
  19. Membrane Microvesicles as Potential Vaccine Candidates.International journal of molecular sciences · 2021
    Review
  20. Biomolecules · 2020
    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

15 authors at 5 institutions in 1 country.

A L CarvalhoGut Microbes and Health Research Programme, Quadram Institute Bioscience, Norwich, UK.
A Miquel-ClopésGut Microbes and Health Research Programme, Quadram Institute Bioscience, Norwich, UK.
U WegmannGut Microbes and Health Research Programme, Quadram Institute Bioscience, Norwich, UK.
E JonesGut Microbes and Health Research Programme, Quadram Institute Bioscience, Norwich, UK.
R StentzGut Microbes and Health Research Programme, Quadram Institute Bioscience, Norwich, UK.
A TelatinGut Microbes and Health Research Programme, Quadram Institute Bioscience, Norwich, UK.
N J WalkerDefence Science and Technology Laboratory, Porton, Salisbury, UK.
W A ButcherDefence Science and Technology Laboratory, Porton, Salisbury, UK.
P J BrownPublic Health England, Porton, Porton, Salisbury, UK.
S HolmesPublic Health England, Porton, Porton, Salisbury, UK.
M J DennisPublic Health England, Porton, Porton, Salisbury, UK.
E D WilliamsonDefence Science and Technology Laboratory, Porton, Salisbury, UK.ORCID 0000-0002-0322-5972
S G P FunnellPublic Health England, Porton, Porton, Salisbury, UK.ORCID 0000-0002-4254-2751
M StockPlant Biotechnology Ltd, Norwich, UK.
S R CardingGut Microbes and Health Research Programme, Quadram Institute Bioscience, Norwich, UK.ORCID 0000-0002-2383-9701
Quadram Institute · GBPublic Health England · GBDefence Science and Technology Laboratory · GBPlant Bioscience Limited (United Kingdom) · GBUniversity of East Anglia · GB

Funding

Biotechnology and Biological Sciences Research Council BB/J004529/1Biotechnology and Biological Sciences Research Council BB/L004291/1Biotechnology and Biological Sciences Research Council BBS/E/F/000PR10355
6 · The paper itself

Abstract

Plague caused by the Gram-negative bacterium, Yersinia pestis, is still endemic in parts of the world today. Protection against pneumonic plague is essential to prevent the development and spread of epidemics. Despite this, there are currently no licensed plague vaccines in the western world. Here we describe the means of delivering biologically active plague vaccine antigens directly to mucosal sites of plague infection using highly stable microvesicles (outer membrane vesicles; OMVs) that are naturally produced by the abundant and harmless human commensal gut bacterium Bacteroides thetaiotaomicron (Bt). Bt was engineered to express major plague protective antigens in its OMVs, specifically Fraction 1 (F1) in the outer membrane and LcrV (V antigen) in the lumen, for targeted delivery to the gastrointestinal (GI) and respiratory tracts in a non-human primate (NHP) host. Our key findings were that Bt OMVs stably expresses F1 and V plague antigens, particularly the V antigen, in the correct, immunogenic form. When delivered intranasally V-OMVs elicited substantive and specific immune and antibody responses, both in the serum [immunoglobulin (Ig)G] and in the upper and lower respiratory tract (IgA); this included the generation of serum antibodies able to kill plague bacteria. Our results also showed that Bt OMV-based vaccines had many desirable characteristics, including: biosafety and an absence of any adverse effects, pathology or gross alteration of resident microbial communities (microbiotas); high stability and thermo-tolerance; needle-free delivery; intrinsic adjuvanticity; the ability to stimulate both humoral and cell-mediated immune responses; and targeting of primary sites of plague infection.

Indexed as

Administration, IntranasalAnimalsAntibodies, BacterialAntigens, BacterialBacterial Outer MembraneBacteroides thetaiotaomicronBioengineeringCell DeathCells, CulturedGastrointestinal MicrobiomeHumansImmunity, CellularImmunity, HumoralImmunoglobulin AImmunoglobulin GMacacaAntibodies, BacterialAntigens, BacterialImmunoglobulin AImmunoglobulin GLcrV protein, YersiniaPlague VaccinePore Forming Cytotoxic Proteinsantibodiesgut bacteriahumoral immunitymucosal vaccinenon-human primatesouter membrane vesiclesplague

Identifiers

PMID30985006
PMCPMC6514708
OpenAlexW2936753094

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.