Evidence map›Paper›PMID 24312658›Full record

ArticlePloS one2013

Pre-clinical development of a recombinant, replication-competent adenovirus serotype 4 vector vaccine expressing HIV-1 envelope 1086 clade C.

Jeff Alexander, Jason Mendy, Lo Vang, Jenny B Avanzini, Fermin Garduno, Darly J Manayani, Glenn Ishioka, Peggy Farness, Li-Hua Ping, Ronald Swanstrom and 8 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.1field-weighted citation impact, top 25% 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, 28 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. HIV vaccinology: 2021 update.Seminars in immunology · 2021
    Review
  9. A Systematic Approach to HIV-1 Vaccine Immunogen Selection.AIDS research and human retroviruses · 2020
    Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Development of Novel Adenoviral Vectors to Overcome Challenges Observed With HAdV-5-based Constructs.Molecular therapy : the journal of the American Society of Gene Therapy · 2016
    Review
  18. Article
  19. Article
  20. 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

18 authors at 4 institutions in 2 countries.

Jeff AlexanderPaxVax Inc, San Diego, California, United States of America.
Jason Mendy
Lo Vang
Jenny B Avanzini
Fermin Garduno
Darly J Manayani
Glenn Ishioka
Peggy Farness
Li-Hua Ping
Ronald Swanstrom
Robert Parks
Hua-Xin Liao
Barton F Haynes
David C Montefiori
Celia LaBranche
Jonathan Smith
Marc Gurwith
Tim Mayall
PaxVax (United States) · USDuke University · USPAX Scientific (United States) · USUniversity of North Carolina at Chapel Hill · US

Funding

Virus biology scientific research support componentUM1AI100645 · NIAID · DUKE UNIVERSITY · PI MONTEFIORI, DAVID C · 2012 to 2018
$204.7M
Oral, replicating Ad4-HIV vaccine development & evaluation in NHP challenge modelR44AI091546 · NIAID · PAXVAX, INC. · PI ALEXANDER, JEFFERY, GURWITH, MARC JOSEPH · 2012 to 2014
$3.0M
Ad4 vectored HIV-Env vaccines with improved immunogenicityR43AI091546 · NIAID · PAXVAX, INC. · PI GURWITH, MARC JOSEPH, MAYALL, TIMOTHY · 2010 to 2010
$300k
NIAID NIH HHS 1R43AI091546-01NIAID NIH HHS AI 100645NIAID NIH HHS R43 AI091546NIAID NIH HHS R44 AI091546NIAID NIH HHS UM1 AI100645PHS HHS HHSN27201100016C
6 · The paper itself

Abstract

backgroundThere is a well-acknowledged need for an effective AIDS vaccine that protects against HIV-1 infection or limits in vivo viral replication. The objective of these studies is to develop a replication-competent, vaccine vector based on the adenovirus serotype 4 (Ad4) virus expressing HIV-1 envelope (Env) 1086 clade C glycoprotein. Ad4 recombinant vectors expressing Env gp160 (Ad4Env160), Env gp140 (Ad4Env140), and Env gp120 (Ad4Env120) were evaluated.

methodsThe recombinant Ad4 vectors were generated with a full deletion of the E3 region of Ad4 to accommodate the env gene sequences. The vaccine candidates were assessed in vitro following infection of A549 cells for Env-specific protein expression and for posttranslational transport to the cell surface as monitored by the binding of broadly neutralizing antibodies (bNAbs). The capacity of the Ad4Env vaccines to induce humoral immunity was evaluated in rabbits for Env gp140 and V1V2-specific binding antibodies, and HIV-1 pseudovirus neutralization. Mice immunized with the Ad4Env160 vaccine were assessed for IFNγ T cell responses specific for overlapping Env peptide sets.

resultsRobust Env protein expression was confirmed by western blot analysis and recognition of cell surface Env gp160 by multiple bNAbs. Ad4Env vaccines induced humoral immune responses in rabbits that recognized Env 1086 gp140 and V1V2 polypeptide sequences derived from 1086 clade C, A244 clade AE, and gp70 V1V2 CASE A2 clade B fusion protein. The immune sera efficiently neutralized tier 1 clade C pseudovirus MW965.26 and neutralized the homologous and heterologous tier 2 pseudoviruses to a lesser extent. Env-specific T cell responses were also induced in mice following Ad4Env160 vector immunization.

conclusionsThe Ad4Env vaccine vectors express high levels of Env glycoprotein and induce both Env-specific humoral and cellular immunity thus supporting further development of this new Ad4 HIV-1 Env vaccine platform in Phase 1 clinical trials.

Indexed as

AdenoviridaeAIDS VaccinesAnimalsCell Lineenv Gene Products, Human Immunodeficiency VirusFemaleHIV-1HumansMaleMiceMutagenesis, Site-DirectedRabbitsAIDS Vaccinesenv Gene Products, Human Immunodeficiency Virus

Identifiers

PMID24312658
PMCPMC3849430
OpenAlexW2028214865

What OpenQuestion holds

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LicenceCC BY
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.