Evidence map›Paper›PMID 25144771›Full record

ArticlePLoS neglected tropical diseases2014

Immunization with Hexon modified adenoviral vectors integrated with gp83 epitope provides protection against Trypanosoma cruzi infection.

Anitra L Farrow, Girish Rachakonda, Linlin Gu, Valentina Krendelchtchikova, Pius N Nde, Siddharth Pratap, Maria F Lima, Fernando Villalta, Qiana L Matthews

Open access · goldAbstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

14 citing papers in PubMed, 21 citations in OpenAlex.

  1. Developing the next-generation of adenoviral vector vaccines.Human vaccines & immunotherapeutics · 2025
    Review
  2. Review
  3. Immunoinformatic construction of an adenovirus-based modular vaccine platform and its application in the design of a SARS-CoV-2 vaccine.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2020
    Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Development of Novel Adenoviral Vectors to Overcome Challenges Observed With HAdV-5-based Constructs.Molecular therapy : the journal of the American Society of Gene Therapy · 2016
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Progress on adenovirus-vectored universal influenza vaccines.Human vaccines & immunotherapeutics · 2015
    Review
  14. 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

9 authors at 2 institutions in 1 country.

Anitra L FarrowDepartment of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Girish RachakondaDepartment of Microbiology and Immunology, School of Medicine, Meharry Medical College, Nashville, Tennessee, United States of America.
Linlin GuDepartment of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Valentina KrendelchtchikovaDepartment of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Pius N NdeDepartment of Microbiology and Immunology, School of Medicine, Meharry Medical College, Nashville, Tennessee, United States of America.
Siddharth PratapDepartment of Microbiology and Immunology, School of Medicine, Meharry Medical College, Nashville, Tennessee, United States of America.
Maria F LimaDepartment of Microbiology and Immunology, School of Medicine, Meharry Medical College, Nashville, Tennessee, United States of America.
Fernando VillaltaDepartment of Microbiology and Immunology, School of Medicine, Meharry Medical College, Nashville, Tennessee, United States of America.
Qiana L MatthewsDepartment of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Center for AIDS Research, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Meharry Medical College · USUniversity of Alabama at Birmingham · US

Funding

The RCMI Program in Health Disparities Research at Meharry Medical College - SupplementU54MD007586 · NIMHD · MEHARRY MEDICAL COLLEGE · PI Maureen Sanderson · 2017 to 2026
$48.2M
Technologies and Resources CoreU54MD007593 · NIMHD · MEHARRY MEDICAL COLLEGE · PI ADUNYAH, SAMUEL EVANS · 2012 to 2018
$24.7M
THE MEHARRY RISE INITIATIVER25GM059994 · NIGMS · MEHARRY MEDICAL COLLEGE · PI MOTLEY-JOHNSON, EVANGELINE D · 1999 to 2021
$23.0M
TrainingU54CA163072 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Karen Marie Winkfield · 2011 to 2026
$20.1M
Translational Pathology CoreU54CA163069 · NCI · MEHARRY MEDICAL COLLEGE · PI BALLARD, BILLY RAY · 2011 to 2025
$18.8M
TRAININGU54CA163066 · NCI · TENNESSEE STATE UNIVERSITY · PI MARGARET M WHALEN · 2011 to 2026
$12.8M
Meharry RCMI Program in Women's Health ResearchG12MD007586 · NIMHD · MEHARRY MEDICAL COLLEGE · PI HILDRETH, JAMES E · 2012 to 2016
$7.8M
Research Training in Cardivascular Biology at MeharryT32HL007737 · NHLBI · MEHARRY MEDICAL COLLEGE · PI MARTIN, PAMELA M · 1993 to 2025
$4.7M
BASIC MECHANISMS IN AIDS PATHOGENESIST32AI007493 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI MORROW, CASEY D · 1995 to 2014
$4.2M
MOLECULAR PARASITOLOGY TRAINING PROGRAMT32AI007281 · NIAID · MEHARRY MEDICAL COLLEGE · PI NDE, PIUS N · 1985 to 2025
$3.2M
Chimeric adenoviruses for an improved HIV vaccineR01AI089337 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI MATTHEWS, QIANA L · 2011 to 2014
$1.4M
Molecular Analysis of Trypanosome InfectionSC1AI080580 · NIAID · MEHARRY MEDICAL COLLEGE · PI VILLALTA, FERNANDO · 2008 to 2010
$1.1M
NCI NIH HHS U54 CA163066NCI NIH HHS U54 CA163069NCI NIH HHS U54 CA163072NHLBI NIH HHS T32 HL007737NIAID NIH HHS 5R01AI089337-04NIAID NIH HHS 5T32AI7493-18NIAID NIH HHS AI007281NIAID NIH HHS AI080580NIAID NIH HHS AI083925NIAID NIH HHS R01 AI089337NIAID NIH HHS SC1 AI080580NIAID NIH HHS SC2 AI083925NIAID NIH HHS T32 AI007281NIAID NIH HHS T32 AI007493NIGMS NIH HHS GM059994NIGMS NIH HHS R25 GM059994NIMHD NIH HHS G12 MD007586NIMHD NIH HHS MD007586NIMHD NIH HHS MD007593NIMHD NIH HHS U54 MD007586NIMHD NIH HHS U54 MD007593
6 · The paper itself

Abstract

backgroundTrypanosoma cruzi is the causative agent of Chagas disease. Chagas disease is an endemic infection that affects over 8 million people throughout Latin America and now has become a global challenge. The current pharmacological treatment of patients is unsuccessful in most cases, highly toxic, and no vaccines are available. The results of inadequate treatment could lead to heart failure resulting in death. Therefore, a vaccine that elicits neutralizing antibodies mediated by cell-mediated immune responses and protection against Chagas disease is necessary. METHODOLOGY/PRINCIPAL

findingsThe "antigen capsid-incorporation" strategy is based upon the display of the T. cruzi epitope as an integral component of the adenovirus' capsid rather than an encoded transgene. This strategy is predicted to induce a robust humoral immune response to the presented antigen, similar to the response provoked by native Ad capsid proteins. The antigen chosen was T. cruzi gp83, a ligand that is used by T. cruzi to attach to host cells to initiate infection. The gp83 epitope, recognized by the neutralizing MAb 4A4, along with His6 were incorporated into the Ad serotype 5 (Ad5) vector to generate the vector Ad5-HVR1-gp83-18 (Ad5-gp83). This vector was evaluated by molecular and immunological analyses. Vectors were injected to elicit immune responses against gp83 in mouse models. Our findings indicate that mice immunized with the vector Ad5-gp83 and challenged with a lethal dose of T. cruzi trypomastigotes confer strong immunoprotection with significant reduction in parasitemia levels, increased survival rate and induction of neutralizing antibodies. CONCLUSIONS/SIGNIFICANCE: This data demonstrates that immunization with adenovirus containing capsid-incorporated T. cruzi antigen elicits a significant anti-gp83-specific response in two different mouse models, and protection against T. cruzi infection by eliciting neutralizing antibodies mediated by cell-mediated immune responses, as evidenced by the production of several Ig isotypes. Taken together, these novel results show that the recombinant Ad5 presenting T. cruzi gp83 antigen is a useful candidate for the development of a vaccine against Chagas disease.

Indexed as

Capsid ProteinsChagas DiseaseTrypanosoma cruziVariant Surface Glycoproteins, TrypanosomaAdenoviridaeAnimalsFemaleGenetic VectorsHEK293 CellsHumansMiceMice, Inbred C57BLProtozoan ProteinsCapsid Proteinshexon capsid protein, AdenovirusProtozoan ProteinsVariant Surface Glycoproteins, Trypanosoma

Identifiers

PMID25144771
PMCPMC4140675
OpenAlexW2043242356

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.