Evidence map›Paper›PMID 20410262›Full record

ArticleJournal of virology2010

Inhibition of in vivo HIV infection in humanized mice by gene therapy of human hematopoietic stem cells with a lentiviral vector encoding a broadly neutralizing anti-HIV antibody.

Aviva Joseph, Jian Hua Zheng, Ken Chen, Monica Dutta, Cindy Chen, Gabriela Stiegler, Renate Kunert, Antonia Follenzi, Harris Goldstein

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
6.8field-weighted citation impact, top 3% 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

63 citing papers in PubMed, 81 citations in OpenAlex.

  1. Trial
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  9. Review
  10. Vector Strategies to Actualize B Cell-Based Gene Therapies.Journal of immunology (Baltimore, Md. : 1950) · 2021
    Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Long-Term Persistence of Anti-HIV Broadly Neutralizing Antibody-Secreting Hematopoietic Cells in Humanized Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2019
    Article
  17. Genetic Strategies for HIV Treatment and Prevention.Molecular therapy. Nucleic acids · 2018
    Review
  18. Review
  19. Article
  20. Humanized Mice as Unique Tools for Human-Specific Studies.Archivum immunologiae et therapiae experimentalis · 2018
    Review

3 more citing papers are in PubMed but not listed here.

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 5 institutions in 4 countries.

Aviva JosephDepartments of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Jian Hua Zheng
Ken Chen
Monica Dutta
Cindy Chen
Gabriela Stiegler
Renate Kunert
Antonia Follenzi
Harris Goldstein
Bipar · FRAlbert Einstein College of Medicine · USBOKU University · ATInstitut thématique Génétique, génomique et bioinformatique · FRPolymun (Austria) · AT

Funding

Immunology/Pathology CoreP30AI051519 · NIAID · YESHIVA UNIVERSITY · PI GOLDSTEIN, HARRIS · 2003 to 2013
$18.6M
Mechanisms of in vivo protection from HIV infectionR01AI067136 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI GOLDSTEIN, HARRIS · 2007 to 2010
$1.6M
NIAID NIH HHS AI51519NIAID NIH HHS AI67136NIAID NIH HHS P30 AI051519NIAID NIH HHS R01 AI067136
6 · The paper itself

Abstract

Due to the inherent immune evasion properties of the HIV envelope, broadly neutralizing HIV-specific antibodies capable of suppressing HIV infection are rarely produced by infected individuals. We examined the feasibility of utilizing genetic engineering to circumvent the restricted capacity of individuals to endogenously produce broadly neutralizing HIV-specific antibodies. We constructed a single lentiviral vector that encoded the heavy and light chains of 2G12, a broadly neutralizing anti-HIV human antibody, and that efficiently transduced and directed primary human B cells to secrete 2G12. To evaluate the capacity of this approach to provide protection from in vivo HIV infection, we used the humanized NOD/SCID/gamma(c)(null) mouse model, which becomes populated with human B cells, T cells, and macrophages after transplantation with human hematopoietic stem cells (hu-HSC) and develops in vivo infection after inoculation with HIV. The plasma of the irradiated NOD/SCID/gamma(c)(null) mice transplanted with hu-HSC transduced with the 2G12-encoding lentivirus contained 2G12 antibody, likely secreted by progeny human lymphoid and/or myeloid cells. After intraperitoneal inoculation with high-titer HIV-1(JR-CSF), mice engrafted with 2G12-transduced hu-HSC displayed marked inhibition of in vivo HIV infection as manifested by a profound 70-fold reduction in plasma HIV RNA levels and an almost 200-fold reduction in HIV-infected human cell numbers in mouse spleens, compared to control hu-HSC-transplanted NOD/SCID/gamma(c)(null) mice inoculated with equivalent high-titer HIV-1(JR-CSF). These results support the potential efficacy of this new gene therapy approach of using lentiviral vectors encoding a mixture of broadly neutralizing HIV antibodies for the treatment of HIV infection, particularly infection with multiple-drug-resistant isolates.

Indexed as

AnimalsAntibodies, NeutralizingAntibodies, ViralGenetic TherapyGenetic VectorsHematopoietic Stem CellsHIV-1HIV InfectionsHumansImmunotherapyLentivirusLentivirus InfectionsMiceMice, Inbred NODMice, SCIDSpleenAntibodies, NeutralizingAntibodies, Viral

Identifiers

PMID20410262
PMCPMC2903239
OpenAlexW2153112971

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.