Evidence map›Paper›PMID 22973033›Full record

ArticleJournal of virology2012

Deletion of specific immune-modulatory genes from modified vaccinia virus Ankara-based HIV vaccines engenders improved immunogenicity in rhesus macaques.

David A Garber, Leigh A O'Mara, Sailaja Gangadhara, Monica McQuoid, Xiugen Zhang, Rui Zheng, Kiran Gill, Meena Verma, Tianwei Yu, Brent Johnson and 6 more

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
2.7field-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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Progress in gene therapy using oncolytic vaccinia virus as vectors.Journal of cancer research and clinical oncology · 2018
    Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Multiple facets of TPP1 in telomere maintenance.Biochimica et biophysica acta · 2014
    Review
  20. 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

16 authors at 2 institutions in 1 country.

David A GarberEmory Vaccine Center, Emory University, Atlanta, Georgia, USA. david.garber@cdc.hhs.gov
Leigh A O'Mara
Sailaja Gangadhara
Monica McQuoid
Xiugen Zhang
Rui Zheng
Kiran Gill
Meena Verma
Tianwei Yu
Brent Johnson
Bing Li
Cynthia A Derdeyn
Chris Ibegbu
John D Altman
Eric Hunter
Mark B Feinberg
Emory University · USUnited States Military Academy · US

Funding

YNPRC NHP CLINICAL MEDICINE RESIDENCY PROGRAM - SUPPLEMENTP51RR000165 · NCRR · EMORY UNIVERSITY · PI ALTMAN, JOHN DAVID · 1985 to 2011
$114.0M
Virology and Molecular Biomarkers CoreP30AI050409 · NIAID · EMORY UNIVERSITY · PI Carlos del Rio · 2002 to 2026
$74.0M
Project Coordination and Product DevelopmentU19AI061728 · NIAID · EMORY UNIVERSITY · PI ALTMAN, JOHN D · 2004 to 2008
$14.3M
NCRR NIH HHS P51 RR000165NIAID NIH HHS P30 AI050409NIAID NIH HHS U19 AI061728
6 · The paper itself

Abstract

Modified vaccinia virus Ankara (MVA) is a safe, attenuated orthopoxvirus that is being developed as a vaccine vector but has demonstrated limited immunogenicity in several early-phase clinical trials. Our objective was to rationally improve the immunogenicity of MVA-based HIV/AIDS vaccines via the targeted deletion of specific poxvirus immune-modulatory genes. Vaccines expressing codon-optimized HIV subtype C consensus Env and Gag antigens were generated from MVA vector backbones that (i) harbor simultaneous deletions of four viral immune-modulatory genes, encoding an interleukin-18 (IL-18) binding protein, an IL-1β receptor, a dominant negative Toll/IL-1 signaling adapter, and CC-chemokine binding protein (MVAΔ4-HIV); (ii) harbor a deletion of an additional (fifth) viral gene, encoding uracil-DNA glycosylase (MVAΔ5-HIV); or (iii) represent the parental MVA backbone as a control (MVA-HIV). We performed head-to-head comparisons of the cellular and humoral immune responses that were elicited by these vectors during homologous prime-boost immunization regimens utilizing either high-dose (2 × 10(8) PFU) or low-dose (1 × 10(7) PFU) intramuscular immunization of rhesus macaques. At all time points, a majority of the HIV-specific T cell responses, elicited by all vectors, were directed against Env, rather than Gag, determinants, as previously observed with other vector systems. Both modified vectors elicited up to 6-fold-higher frequencies of HIV-specific CD8 and CD4 T cell responses and up to 25-fold-higher titers of Env (gp120)-specific binding (nonneutralizing) antibody responses that were relatively transient in nature. While the correlates of protection against HIV infection remain incompletely defined, our results indicate that the rational deletion of specific genes from MVA vectors can positively alter their cellular and humoral immunogenicity profiles in nonhuman primates.

Indexed as

AIDS VaccinesAnimalsAntibody FormationDose-Response Relationship, Drugenv Gene Products, Human Immunodeficiency VirusFemalegag Gene Products, Human Immunodeficiency VirusGene DeletionGenetic VectorsInjections, IntramuscularIntercellular Signaling Peptides and ProteinsMacaca mulattaReceptors, ChemokineReceptors, Interleukin-1T-LymphocytesVaccines, DNAAIDS Vaccinesenv Gene Products, Human Immunodeficiency Virusgag Gene Products, Human Immunodeficiency VirusIntercellular Signaling Peptides and Proteinsinterleukin-18 binding proteinMVA vaccineReceptors, ChemokineReceptors, Interleukin-1Vaccines, DNAViral Vaccines

Identifiers

PMID22973033
PMCPMC3497691
OpenAlexW2162143446

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.