Evidence map›Paper›PMID 24291126›Full record

ArticleJournal of immunological methods2014

Development of a luciferase based viral inhibition assay to evaluate vaccine induced CD8 T-cell responses.

Marloes A Naarding, Natalia Fernandez, John C Kappes, Peter Hayes, Tina Ahmed, Mert Icyuz, Tara G Edmonds, Philip Bergin, Omu Anzala, Tomas Hanke and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of immunological methods, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 20% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. HTLV-2 Enhances CD8Viruses · 2022
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. TheF1000Research · 2021
    Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Broad HIV-1 inhibition in vitro by vaccine-elicited CD8(+) T cells in African adults.Molecular therapy. Methods & clinical development · 2016
    Article
  18. Article
  19. Article
  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

15 authors at 5 institutions in 3 countries.

Marloes A NaardingHuman Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College London, Chelsea and Westminster Hospital, SW10 9NH London, United Kingdom.
Natalia FernandezHuman Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College London, Chelsea and Westminster Hospital, SW10 9NH London, United Kingdom.
John C KappesDepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Birmingham Veterans Affairs Medical Center, Research Service, Birmingham, AL 35233, USA.
Peter HayesHuman Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College London, Chelsea and Westminster Hospital, SW10 9NH London, United Kingdom.
Tina AhmedMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, United Kingdom; The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.
Mert IcyuzDepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Tara G EdmondsDepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Philip BerginHuman Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College London, Chelsea and Westminster Hospital, SW10 9NH London, United Kingdom.
Omu AnzalaKenya AIDS Vaccine Initiative (KAVI), Nairobi, Kenya.
Tomas HankeMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, United Kingdom; The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.
Lorna ClarkHuman Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College London, Chelsea and Westminster Hospital, SW10 9NH London, United Kingdom.
Josephine H CoxHuman Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College London, Chelsea and Westminster Hospital, SW10 9NH London, United Kingdom. Electronic address: jcox@iavi.org.
Emmanuel CormierHuman Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College London, Chelsea and Westminster Hospital, SW10 9NH London, United Kingdom.
Christina OchsenbauerDepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Jill GilmourHuman Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College London, Chelsea and Westminster Hospital, SW10 9NH London, United Kingdom.
Imperial College London · GBUniversity of Alabama at Birmingham · USChelsea and Westminster Hospital · GBUniversity of Oxford · GBKenya AIDS Vaccine Initiative · KE

Funding

Virology CoreP30AI027767 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Latesha Ellen Elopre · 1988 to 2026
$84.1M
Viral and Host Determinants of HIV-1 TransmissionU01AI067854 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F · 2005 to 2005
$14.9M
Medical Research Council G0701669Medical Research Council MC_U137884179NIAID NIH HHS P30 AI027767NIAID NIH HHS P30 AI 27767NIAID NIH HHS U01 AI067854NIAID NIH HHS U01-AI067854
6 · The paper itself

Abstract

Emergence of SIV and HIV specific CD8 T cells has been shown to correlate with control of in vivo replication. Poor correlation between IFN-γ ELISPOT responses and in vivo control of the virus has triggered the development of more relevant assays to assess functional HIV-1 specific CD8 T-cell responses for the evaluation and prioritization of new HIV-1 vaccine candidates. We previously established a viral inhibition assay (VIA) that measures the ability of vaccine-induced CD8 T-cell responses to inhibit viral replication in autologous CD4 T cells. In this assay, viral replication is determined by measuring p24 in the culture supernatant. Here we describe the development of a novel VIA, referred to as IMC LucR VIA that exploits replication-competent HIV-1 infectious molecular clones (IMCs) in which the complete proviral genome is strain-specific and which express the Renilla luciferase (LucR) gene to determine viral growth and inhibition. The introduction of the luciferase readout does provide significant improvement of the read out time. In addition to switching to the LucR read out, changes made to the overall protocol resulted in the miniaturization of the assay from a 48 to a 96-well plate format, which preserved sample and allowed for the introduction of replicates. The overall assay time was reduced from 13 to 8 days. The assay has a high degree of specificity, and the previously observed non-specific background inhibition in cells from HIV-1 negative volunteers has been reduced dramatically. Importantly, we observed an increase in positive responses, indicating an improvement in sensitivity compared to the original VIA. Currently, only a limited number of "whole-genome" IMC-LucR viruses are available and our efforts will focus on expanding the panel to better evaluate anti-viral breadth. Overall, we believe the IMC LucR VIA provides a platform to assess functional CD8 T-cell responses in large-scale clinical trial testing, which will enhance the ability to select the most promising HIV-1 vaccine candidates capable of controlling HIV-1 replication in vivo.

Indexed as

Genes, ReporterVirus ReplicationAIDS VaccinesAutomation, LaboratoryCD8-Positive T-LymphocytesCell LineGuideline AdherenceHigh-Throughput Screening AssaysHIV-1HIV Core Protein p24HIV InfectionsHumansLuciferases, RenillaMiniaturizationObserver VariationPractice Guidelines as TopicAIDS VaccinesHIV Core Protein p24Luciferases, Renillap24 protein, Human Immunodeficiency Virus Type 1CD8 T cellsHIVInfectious molecular clonesRenilla reniformis luciferaseVaccine Clinical trialViral inhibition assay

Identifiers

PMID24291126
PMCPMC4236027
OpenAlexW2083662482

What OpenQuestion holds

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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.