Evidence map›Paper›PMID 14963160›Full record

ArticleJournal of virology2004

Modification to the capsid of the adenovirus vector that enhances dendritic cell infection and transgene-specific cellular immune responses.

Stefan Worgall, Annette Busch, Michael Rivara, David Bonnyay, Philip L Leopold, Robert Merritt, Neil R Hackett, Peter W Rovelink, Joseph T Bruder, Thomas J Wickham and 2 more

Abstract read
In one paragraph

Article in Journal of virology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
7.8field-weighted citation impact, top 2% 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

32 citing papers in PubMed, 79 citations in OpenAlex.

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  8. Biodistribution and inflammatory profiles of novel penton and hexon double-mutant serotype 5 adenoviruses.Journal of controlled release : official journal of the Controlled Release Society · 2012
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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

12 authors at 2 institutions in 1 country.

Stefan WorgallDepartment of Genetic Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA. geneticmedicine@med.cornell.edu
Annette Busch
Michael Rivara
David Bonnyay
Philip L Leopold
Robert Merritt
Neil R Hackett
Peter W Rovelink
Joseph T Bruder
Thomas J Wickham
Imi Kovesdi
Ronald G Crystal
GenVec · USRockefeller University · US

Funding

VEGF VECTOR TO ISCHEMIC MYOCARDIUM W/DIFFUSE CORONARY DISEASEM01RR000047 · NCRR · WEILL MEDICAL COLL OF CORNELL UNIV · PI MCQUIGGAN, MARGARET M · 1985 to 2007
$36.4M
WEILL CORNELL PROGRAM OF EXCELLENCE IN GENE THERAPYU01HL066952 · NHLBI · WEILL MEDICAL COLLEGE OF CORNELL UNIV · PI CRYSTAL, RONALD G · 2000 to 2005
$15.9M
NCRR NIH HHS M01 RR000047NCRR NIH HHS M01RR00047NHLBI NIH HHS U01 HL066952NHLBI NIH HHS U01 HL66952
6 · The paper itself

Abstract

Adenovirus (Ad) gene transfer vectors can be used to transfer and express antigens and function as strong adjuvants and thus are useful platforms for the development of genetic vaccines. Based on the hypothesis that Ad vectors with enhanced infectibility of dendritic cells (DC) may be able to evoke enhanced immune responses against antigens encoded by the vector in vivo, the present study analyzes the vaccine potential of an Ad vector expressing beta-galactosidase as a model antigen and genetically modified with RGD on the fiber knob [AdZ.F(RGD)] to more selectively infect DC and consequently enhance immunity against the beta-galactosidase antigen. Infection of murine DC in vitro with AdZ.F(RGD) showed an eightfold-increased transgene expression following infection compared to AdZ (also expressing beta-galactosidase, but with a wild-type capsid). Binding, cellular uptake, and trafficking in DC were also increased with AdZ.F(RGD) compared to AdZ. To determine whether AdZ.F(RGD) could evoke enhanced immune responses to beta-galactosidase in vivo, C57BL/6 mice were immunized with AdZ.F(RGD) or AdZ subcutaneously via the footpad. Humoral responses with both vectors were comparable, with similar anti-beta-galactosidase antibody levels following vector administration. However, cellular responses to beta-galactosidase were significantly enhanced, with the frequency of CD4(+) as well as the CD8(+) beta-galactosidase-specific gamma interferon response in cells isolated from the draining lymph nodes increased following immunization with AdZ.F(RGD) compared to Ad.Z (P < 0.01). Importantly, this enhanced cellular immune response of the AdZ.F(RGD) vector was sufficient to evoke enhanced inhibition of the growth of preexisting tumors expressing beta-galactosidase: BALB/c mice implanted with the CT26 syngeneic beta-galactosidase-expressing colon carcinoma cell line and subsequently immunized with AdZ.F(RGD) showed decreased tumor growth and improved survival compared to mice immunized with AdZ. These data demonstrate that addition of an RGD motif to the Ad fiber knob increases the infectibility of DC and leads to enhanced cellular immune responses to the Ad-transferred transgene, suggesting that the RGD capsid modification may be useful in developing Ad-based vaccines.

Indexed as

AdenoviridaeAnimalsAntibody Formationbeta-GalactosidaseCancer VaccinesCapsid ProteinsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesDendritic CellsGenes, ReporterGenetic TherapyGenetic VectorsImmunity, CellularImmunizationMiceMice, Inbred C57BLbeta-GalactosidaseCancer VaccinesCapsid Proteins

Identifiers

PMID14963160
PMCPMC369215
OpenAlexW2071710058

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.