Evidence map›Paper›PMID 27886660›Full record

ArticleClinical and experimental immunology2017

Evaluation of the safety and adjuvant effect of a detoxified listeriolysin O mutant on the humoral response to dengue virus antigens.

K G Hernández-Flores, A L Calderón-Garcidueñas, G Mellado-Sánchez, R Ruiz-Ramos, L A Sánchez-Vargas, P Thomas-Dupont, I Y Izaguirre-Hernández, J Téllez-Sosa, J Martínez-Barnetche, L Wood and 4 more

Open access · greenAbstract read
In one paragraph

Article in Clinical and experimental immunology, 2017. 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
0.3field-weighted citation impact, top 28% 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

3 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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

14 authors at 4 institutions in 2 countries.

K G Hernández-FloresInstituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz City, Veracruz, México.
A L Calderón-GarcidueñasInstituto de Medicina Forense, Universidad Veracruzana, Boca del Río Veracruz, México.
G Mellado-SánchezInstituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz City, Veracruz, México.
R Ruiz-RamosInstituto de Medicina Forense, Universidad Veracruzana, Boca del Río Veracruz, México.
L A Sánchez-VargasInstituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz City, Veracruz, México.
P Thomas-DupontInstituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz City, Veracruz, México.
I Y Izaguirre-HernándezInstituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz City, Veracruz, México.
J Téllez-SosaDepartamento de Inmunología, Instituto Nacional de Salud Pública (INSP), Centro de Investigación Sobre Enfermedades Infecciosas (CISEI), Cuernavaca, México.
J Martínez-BarnetcheDepartamento de Inmunología, Instituto Nacional de Salud Pública (INSP), Centro de Investigación Sobre Enfermedades Infecciosas (CISEI), Cuernavaca, México.
L WoodDepartment of Microbiology, University of Pennsylvania, Philadelphia, PA, USA.
Y PatersonDepartment of Microbiology, University of Pennsylvania, Philadelphia, PA, USA.
L Cedillo-BarrónDepartamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados IPN, Ciudad de México, México.
O López-FrancoCentro de Estudios y Servicios en Salud. Universidad Veracruzana, Veracruz City, Veracruz, México.
H Vivanco-CidInstituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz City, Veracruz, México.
Universidad Veracruzana · MXInstituto Nacional de Salud Pública · MXUniversity of Pennsylvania · USCenter for Research and Advanced Studies of the National Polytechnic Institute · MX

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Listeriolysin O (LLO) has been proposed as a potential carrier or adjuvant molecule in the vaccination field. However, the cytotoxic and pro-apoptotic effects of LLO are the major limitations for this purpose. Here, we have performed a preclinical safety evaluation and characterized a new potential adjuvant application for a non-cytolytic LLO mutant (dtLLO) to enhance and modulate the immune response against the envelope (E) protein from dengue virus. In addition, we have studied the adjuvant effects of dtLLO on human immune cells and the role of membrane cholesterol for the binding and proinflammatory property of the toxoid. Our in-vivo results in the murine model confirmed that dtLLO is a safer molecule than wild-type LLO (wtLLO), with a significantly increased survival rate for mice challenged with dtLLO compared with mice challenged with wtLLO (P < 0·001). Histopathological analysis showed non-toxic effects in key target organs such as brain, heart, liver, spleen, kidney and lung after challenge with dtLLO. In vitro, dtLLO retained the capacity of binding to plasma membrane cholesterol on the surface of murine and human immune cells. Immunization of 6-8-week-old female BALB/c mice with a combination of dtLLO mixed with E protein elicited a robust specific humoral response with isotype diversification of immunoglobulin (Ig)G antibodies (IgG1 and IgG2a). Finally, we demonstrated that cholesterol and lipid raft integrity are required to induce a proinflammatory response by human cells. Taken together, these findings support a potential use of the dtLLO mutant as a safe and effective adjuvant molecule in vaccination.

Indexed as

Adjuvants, ImmunologicImmunity, HumoralAnimalsAntibodies, ViralAntibody SpecificityAntigens, ViralBacterial ToxinsCholesterolCytokinesDendritic CellsDengueDengue VirusDisease Models, AnimalFemaleHeat-Shock ProteinsHemolysin ProteinsAdjuvants, ImmunologicAntibodies, ViralAntigens, ViralBacterial ToxinsCholesterolCytokinesHeat-Shock ProteinsHemolysin ProteinshlyA protein, Listeria monocytogenesInflammation MediatorsMembrane LipidsMutant Proteinsadjuvantcholesteroldenguelisteriolysin O

Identifiers

PMID27886660
PMCPMC5343344
OpenAlexW2559665422

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.