Evidence map›Paper›PMID 25444812›Full record

ArticleVaccine2015

Autologous aldrithiol-2-inactivated HIV-1 combined with polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose as a vaccine platform for therapeutic dendritic cell immunotherapy.

Elizabeth Miller, Meredith Spadaccia, Rachel Sabado, Elena Chertova, Julian Bess, Charles Mac Trubey, Rose Marie Holman, Andres Salazar, Jeffrey Lifson, Nina Bhardwaj

Abstract read
In one paragraph

Article in Vaccine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.3field-weighted citation impact, top 43% 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

4 citing papers in PubMed, 10 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. 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

10 authors at 3 institutions in 1 country.

Elizabeth MillerIcahn School of Medicine at Mount Sinai, Division of Infectious Diseases, New York, NY, USA. Electronic address: elizabeth.a.miller@mssm.edu.
Meredith SpadacciaIcahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, USA.
Rachel SabadoIcahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, USA.
Elena ChertovaAIDS and Cancer Virus Program Inc., Frederick, MD, USA.
Julian BessAIDS and Cancer Virus Program Inc., Frederick, MD, USA.
Charles Mac TrubeyAIDS and Cancer Virus Program Inc., Frederick, MD, USA.
Rose Marie HolmanIcahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, USA.
Andres SalazarOncovir Inc., Washington, DC, USA.
Jeffrey LifsonAIDS and Cancer Virus Program Inc., Frederick, MD, USA.
Nina BhardwajIcahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, USA.
Tisch Cancer InstituteIcahn School of Medicine at Mount Sinai · USOncovir (United States) · US

Funding

Thymic output, lymphocyte activation and turnoverP01AI057127 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI VALENTINE, FRED T · 2004 to 2009
$9.0M
Modulating anti-HIV immunity by plasmacytoid dendritic cellsR01AI081848 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BHARDWAJ, NINA · 2010 to 2021
$4.5M
Induction of Immunity by Non-Replicating HIV-1R37AI044628 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BHARDWAJ, NINA · 2004 to 2014
$4.2M
Use of a Novel Antigen Loading Platform for Dendritic Cell-Based HIV VaccinesK08AI084578 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MILLER, ELIZABETH ANNE · 2009 to 2013
$658k
NIAID Clinical Trial Planning GrantR34AI097000 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BHARDWAJ, NINA · 2011 to 2011
$286k
NIAID NIH HHS K08 AI084578NIAID NIH HHS K08 AI84578NIAID NIH HHS P01 AI057127NIAID NIH HHS P01AI057127NIAID NIH HHS R01 AI081848NIAID NIH HHS R34 AI097000NIAID NIH HHS R37 AI044628PHS HHS U01 A1067854
6 · The paper itself

Abstract

Therapeutic interventions for HIV-1 that successfully augment adaptive immunity to promote killing of infected cells may be a requisite component of strategies to reduce latent cellular reservoirs. Adoptive immunotherapies utilizing autologous monocyte-derived dendritic cells (DCs) that have been activated and antigen loaded ex vivo may serve to circumvent defects in DC function that are present during HIV infection in order to enhance adaptive immune responses. Here we detail the clinical preparation of DCs loaded with autologous aldrithiol-2 (AT-2)-inactivated HIV that have been potently activated with the viral mimic, Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (Poly-ICLC). HIV is first propagated from CD4+ T cells from HIV-infected donors and then rendered non-replicative by chemical inactivation with aldrithiol-2 (AT-2), purified, and quantified. Viral inactivation is confirmed through measurement of Tat-regulated β-galactosidase reporter gene expression following infection of TZM-bl cells. In-process testing for sterility, mycoplasma, LPS, adventitious agents, and removal of AT-2 is performed on viral preparations. Autologous DCs are generated and pulsed with autologous AT-2-inactivated virus and simultaneously stimulated with Poly-ICLC to constitute the final DC vaccine product. Phenotypic identity, maturation, and induction of HIV-specific adaptive immune responses are confirmed via flow cytometric analysis of DCs and cocultured autologous CD4+ and CD8+ T cells. Lot release criteria for the DC vaccine have been defined in accordance with Good Manufacturing Practice (GMP) guidelines. The demonstrated feasibility of this approach has resulted in approval by the FDA for investigational use in antiretroviral (ART) suppressed individuals. We discuss how this optimized DC formulation may enhance the quality of anti-HIV adaptive responses beyond what has been previously observed during DC immunotherapy trials for HIV infection.

Indexed as

Adaptive Immunity2,2'-DipyridylAIDS Vaccinesbeta-GalactosidaseCarboxymethylcellulose SodiumCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell LineDendritic CellsDisulfidesHIV-1HIV InfectionsHumansImmunotherapy, AdoptivePoly I-CPolylysine2,2'-Dipyridyl2,2'-dipyridyl disulfideAIDS Vaccinesbeta-GalactosidaseCarboxymethylcellulose SodiumDisulfidesPoly I-Cpoly ICLCPolylysineDendritic cellHIV-1Poly-ICLCTherapeutic vaccine

Identifiers

PMID25444812
PMCPMC4272884
OpenAlexW2092074459

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.