Evidence map›Paper›PMID 24943382›Full record

ArticleClinical and vaccine immunology : CVI2014

Hexon hypervariable region-modified adenovirus type 5 (Ad5) vectors display reduced hepatotoxicity but induce T lymphocyte phenotypes similar to Ad5 vectors.

Jeffrey E Teigler, Pablo Penaloza-MacMaster, Rebecca Obeng, Nicholas M Provine, Rafael A Larocca, Erica N Borducchi, Dan H Barouch

Open access · diamondAbstract read
In one paragraph

Article in Clinical and vaccine immunology : CVI, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.9field-weighted citation impact, top 13% 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

9 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
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  4. Immunoinformatic construction of an adenovirus-based modular vaccine platform and its application in the design of a SARS-CoV-2 vaccine.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2020
    Article
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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

7 authors at 2 institutions in 1 country.

Jeffrey E TeiglerCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Pablo Penaloza-MacMasterCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Rebecca ObengCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Nicholas M ProvineCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Rafael A LaroccaCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Erica N BorducchiCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Dan H BarouchCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA Ragon Institute of MGH, MIT, and Harvard, Boston, Massachusetts, USA dbarouch@bidmc.harvard.edu.
Beth Israel Deaconess Medical Center · USRagon Institute of MGH, MIT and Harvard · US

Funding

Preclinical Evaluation of Novel Adenovirus Prime-Boost HIV-1 VaccineU19AI078526 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BAROUCH, DAN H. · 2008 to 2012
$44.0M
Preclinical Evaluation of Novel Ad/MVA and Ad/Protein HIV-1 VaccinesU19AI096040 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI SEAMAN, MICHAEL SCOTT · 2012 to 2016
$18.0M
MOLECULAR BASIS OF VIRAL INFECTIVITYT32AI007245 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Aaron Gregory Schmidt · 1985 to 2026
$11.3M
Multidisciplinary HIV Training ProgramT32AI007387 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel R. Kuritzkes · 1990 to 2026
$8.8M
NIAID NIH HHS AI007245NIAID NIH HHS AI078526NIAID NIH HHS AI096040NIAID NIH HHS T32 AI007245NIAID NIH HHS T32 AI007387NIAID NIH HHS T32AI07387NIAID NIH HHS U19 AI078526NIAID NIH HHS U19 AI096040
6 · The paper itself

Abstract

Hexon modification of adenovirus type 5 (Ad5) vectors with the hypervariable regions (HVRs) of Ad48 has been shown to allow Ad5HVR48 vectors to circumvent the majority of the preexisting Ad5-neutralizing antibodies. However, it remains unclear whether modifying hexon HVRs impacts innate or adaptive immune responses elicited by this vector. In this study, we investigated the influence of the HVR substitution of Ad5 on innate and adaptive immune responses following vaccination. Ad5HVR48 displayed an intermediate level of innate immune cytokines and chemokines relative to those of Ad5 and Ad48, consistent with its chimeric nature. Hepatotoxicity was observed after Ad5 immunization but not after Ad5HVR48 or Ad48 immunization. However, the CD8(+) T-cell responses elicited by Ad5HVR48 vectors displayed a partially exhausted phenotype, as evidenced by the sustained expression of programmed death 1 (PD-1), decreased effector-to-central memory conversion, and reduced memory recall responses, similar to those elicited by Ad5 vectors and in contrast to those induced by Ad48 vectors. Taken together, these results indicate that although Ad5HVR48 largely bypasses preexisting Ad5 neutralizing antibodies and shows reduced hepatotoxicity compared to that of Ad5, it induces adaptive immune phenotypes that are functionally exhausted similar to those elicited by Ad5.

Indexed as

Adaptive ImmunityAdenoviridaeAnimalsAntibodies, NeutralizingAntigens, ViralCapsid ProteinsCD8-Positive T-LymphocytesChimeraGenetic VectorsImmune EvasionImmunity, InnateImmunologic MemoryInterferon-gammaInterleukin-2LiverMiceAntibodies, NeutralizingAntigens, ViralCapsid Proteinshexon capsid protein, AdenovirusInterferon-gammaInterleukin-2Pdcd1 protein, mouseProgrammed Cell Death 1 Receptor

Identifiers

PMID24943382
PMCPMC4135912
OpenAlexW2127952975

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.