Evidence map›Paper›PMID 19665799›Full record

ArticleMolecular immunology2009

Preclinical evaluation of innate immunity to baculovirus gene therapy vectors in whole human blood.

Lindsay J Georgopoulos, Graciela Elgue, Javier Sanchez, Vincent Dussupt, Paola Magotti, John D Lambris, Thomas H Tötterman, Norman J Maitland, Bo Nilsson

Abstract read
In one paragraph

Article in Molecular immunology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

12 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Baculovirus: an insect-derived vector for diverse gene transfer applications.Molecular therapy : the journal of the American Society of Gene Therapy · 2013
    Review
  9. Article
  10. Review
  11. Screening of complement inhibitors: shielded baculoviruses increase the safety and efficacy of gene delivery.Molecular therapy : the journal of the American Society of Gene Therapy · 2010
    Article
  12. Review
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 3 institutions in 3 countries.

Lindsay J GeorgopoulosYCR Cancer Research Unit, Department of Biology (Area 13), University of York, Heslington, York YO10 5DD, UK. ljs8@york.ac.uk
Graciela Elgue
Javier Sanchez
Vincent Dussupt
Paola Magotti
John D Lambris
Thomas H Tötterman
Norman J Maitland
Bo Nilsson
Uppsala University Hospital · SEUniversity of York · GBUniversity of Pennsylvania · US

Funding

STRUCTURAL-FUNCTIONAL ANALYSIS OF COMPSTATINR01GM062134 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI LAMBRIS, JOHN D · 2001 to 2010
$2.5M
Computer Aided Design of Complement TherapeuticsR24GM069736 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI LAMBRIS, JOHN D · 2004 to 2007
$1.8M
Biomaterial-induced complement activationR01EB003968 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI LAMBRIS, JOHN D · 2005 to 2008
$1.0M
Medical Research Council G0900871NIBIB NIH HHS 5-R01-EB-003968NIBIB NIH HHS R01 EB003968NIGMS NIH HHS GM069736NIGMS NIH HHS GM-62134NIGMS NIH HHS R01 GM062134NIGMS NIH HHS R24 GM069736
6 · The paper itself

Abstract

Interactions of gene therapy vectors with human blood components upon intravenous administration have a significant effect on vector efficacy and patient safety. Here we describe methods to evaluate these interactions and their effects in whole human blood, using baculovirus vectors as a model. Opsonisation of baculovirus particles by binding of IgM and C3b was demonstrated, which is likely to be the cause of the significant blood cell-associated virus that was detected. Preventing formation of the complement C5b-9 (membrane attack) complex maintained infectivity of baculovirus particles as shown by studying the effects of two specific complement inhibitors, Compstatin and a C5a receptor antagonist. Formation of macroscopic blood clots after 4h was prevented by both complement inhibitors. Pro- and anti-inflammatory cytokines Il-1beta, IL-6, IL-8 and TNF-alpha were produced at variable levels between volunteers and complement inhibitors showed patient-specific effects on cytokine levels. Whilst both complement inhibitors could play a role in protecting patients from aggressive inflammatory reactions, only Compstatin maintained virus infectivity. We conclude that this ex vivo model, used here for the first time with infectious agents, is a valuable tool in evaluating human innate immune responses to gene therapy vectors or to predict the response of individual patients as part of a clinical trial or treatment. The use of complement inhibitors for therapeutic viruses should be considered on a patient-specific basis.

Indexed as

Genetic TherapyImmunity, InnateBaculoviridaeComplement C3bComplement C5aComplement Membrane Attack ComplexCytokinesGenetic VectorsHumansImmunoassayImmunoglobulin MPeptides, CyclicC5aRADComplement C3bComplement C5aComplement Membrane Attack ComplexcompstatinCytokinesImmunoglobulin MPeptides, Cyclic

Identifiers

PMID19665799
PMCPMC2767513
OpenAlexW2141929321

What OpenQuestion holds

Textmetadata
LicenceTDM
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.