Evidence map›Paper›PMID 22132227›Full record

ArticlePloS one2011

Design and analysis of rhesus cytomegalovirus IL-10 mutants as a model for novel vaccines against human cytomegalovirus.

Naomi J Logsdon, Meghan K Eberhardt, Christopher E Allen, Peter A Barry, Mark R Walter

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.6field-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

15 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Neutralization of rhesus cytomegalovirus IL-10 reduces horizontal transmission and alters long-term immunity.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  5. Review
  6. Article
  7. Article
  8. Exploiting viral natural history for vaccine development.Medical microbiology and immunology · 2015
    Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. 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

5 authors at 2 institutions in 1 country.

Naomi J LogsdonDepartment of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Meghan K Eberhardt
Christopher E Allen
Peter A Barry
Mark R Walter
University of Alabama at Birmingham · USUniversity of California, Davis · US

Funding

ZONA PELLUCIDA PEPTIDES AS IMMUNOCONTRACEPTIVE ANTIGENSP51RR000169 · NCRR · UNIVERSITY OF CALIFORNIA DAVIS · PI HYDE, DALLAS MELVIN · 1985 to 2011
$126.2M
Prevention of Primary HCMV Infection by Vaccinating against HCMV-Encoded IL-10R01AI049342 · NIAID · UNIVERSITY OF CALIFORNIA DAVIS · PI BARRY, PETER A, WALTER, MARK R · 2002 to 2017
$6.9M
STRUCTURE STUDIES ON PROTEINS THAT MODULATE IL-10 ACTIONR01AI047300 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI WALTER, MARK R · 2001 to 2011
$3.4M
NCRR NIH HHS P51 RR000169NCRR NIH HHS RR00169NIAID NIH HHS R01 AI047300NIAID NIH HHS R01 AI049342NIAID NIH HHS R01 AI49342
6 · The paper itself

Abstract

backgroundHuman cytomegalovirus (HCMV) expresses a viral ortholog (CMVIL-10) of human cellular interleukin-10 (cIL-10). Despite only ∼26% amino acid sequence identity, CMVIL-10 exhibits comparable immunosuppressive activity with cIL-10, attenuates HCMV antiviral immune responses, and contributes to lifelong persistence within infected hosts. The low sequence identity between CMVIL-10 and cIL-10 suggests vaccination with CMVIL-10 may generate antibodies that specifically neutralize CMVIL-10 biological activity, but not the cellular cytokine, cIL-10. However, immunization with functional CMVIL-10 might be detrimental to the host because of its immunosuppressive properties. METHODS AND

findingsStructural biology was used to engineer biologically inactive mutants of CMVIL-10 that would, upon vaccination, elicit a potent immune response to the wild-type viral cytokine. To test the designed proteins, the mutations were incorporated into the rhesus cytomegalovirus (RhCMV) ortholog of CMVIL-10 (RhCMVIL-10) and used to vaccinate RhCMV-infected rhesus macaques. Immunization with the inactive RhCMVIL-10 mutants stimulated antibodies against wild-type RhCMVIL-10 that neutralized its biological activity, but did not cross-react with rhesus cellular IL-10.

conclusionThis study demonstrates an immunization strategy to neutralize RhCMVIL-10 biological activity using non-functional RhCMVIL-10 antigens. The results provide the methodology for targeting CMVIL-10 in vaccine, and therapeutic strategies, to nullify HCMV's ability to (1) skew innate and adaptive immunity, (2) disseminate from the site of primary mucosal infection, and (3) establish a lifelong persistent infection.

Indexed as

Drug DesignModels, ImmunologicalAmino Acid SequenceAnimalsAntibodies, NeutralizingCell ProliferationCross ReactionsCytomegalovirusCytomegalovirus VaccinesHumansImmunizationInterleukin-10Interleukin-10 Receptor alpha SubunitInterleukin-12Leukocytes, MononuclearMacaca mulattaAntibodies, NeutralizingCytomegalovirus VaccinesInterleukin-10Interleukin-10 Receptor alpha SubunitInterleukin-12Mutant Proteins

Identifiers

PMID22132227
PMCPMC3221699
OpenAlexW2085833371

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.