Evidence map›Paper›PMID 32098811›Full record

ArticlemBio2020

A Lassa Fever Live-Attenuated Vaccine Based on Codon Deoptimization of the Viral Glycoprotein Gene.

Yingyun Cai, Chengjin Ye, Benson Cheng, Aitor Nogales, Masaharu Iwasaki, Shuiqing Yu, Kurt Cooper, David X Liu, Randy Hart, Ricky Adams and 7 more

Open access · goldAbstract read
In one paragraph

Article in mBio, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 15% 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

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

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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

17 authors at 3 institutions in 1 country.

Yingyun CaiIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA.ORCID 0000-0002-1101-0920
Chengjin YeDepartment of Microbiology and Immunology, University of Rochester, Rochester, New York, USA.
Benson ChengDepartment of Microbiology and Immunology, University of Rochester, Rochester, New York, USA.
Aitor NogalesDepartment of Microbiology and Immunology, University of Rochester, Rochester, New York, USA.
Masaharu IwasakiDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA.
Shuiqing YuIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA.ORCID 0000-0002-9473-566X
Kurt CooperIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA.
David X LiuIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA.
Randy HartIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA.
Ricky AdamsIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA.
Tyler BradyIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA.
Elena N PostnikovaIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA.ORCID 0000-0002-0275-2148
Jonathan KurtzIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA.
Marisa St ClaireIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA.ORCID 0000-0001-5493-6187
Jens H KuhnIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA.ORCID 0000-0002-7800-6045
Juan Carlos de la TorreDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA.
Luis Martínez-SobridoDepartment of Microbiology and Immunology, University of Rochester, Rochester, New York, USA luis_martinez@urmc.rochester.edu.ORCID 0000-0001-7084-0804
National Institutes of Health · USUniversity of Rochester · USScripps Research Institute · US

Funding

A General Molecular Strategy for Attenuation of Human Pathogenic ArenavirusesR21AI121840 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI DE LA TORRE, JUAN C. · 2016 to 2017
$529k
Attenuation Of Lassa Virus Via Codon Deoptimization​R21AI135284 · NIAID · UNIVERSITY OF ROCHESTER · PI MARTINEZ-SOBRIDO, LUIS · 2018 to 2019
$522k
NIAID NIH HHS HHSN272200700016INIAID NIH HHS R21 AI121840NIAID NIH HHS R21 AI135284
6 · The paper itself

Abstract

Lassa virus (LASV) is endemic in Western Africa and is estimated to infect hundreds of thousands of individuals annually. A considerable number of these infections result in Lassa fever (LF), which is associated with significant morbidity and a case-fatality rate as high as 69% among hospitalized confirmed patients. U.S. Food and Drug Administration-approved LF vaccines are not available. Current antiviral treatment is limited to off-label use of a nucleoside analogue, ribavirin, that is only partially effective and associated with significant side effects. We generated and characterized a recombinant LASV expressing a codon-deoptimized (CD) glycoprotein precursor gene (GPC), rLASV-GPC/CD. Comparison of growth kinetics and peak titers showed that rLASV-GPC/CD is slightly attenuated in cell culture compared to wild-type (WT) recombinant LASV (rLASV-WT). However, rLASV-GPC/CD is highly attenuated in strain 13 and Hartley guinea pigs, as reflected by the absence of detectable clinical signs in animals inoculated with rLASV-GPC/CD. Importantly, a single subcutaneous dose of rLASV-GPC/CD provides complete protection against an otherwise lethal exposure to LASV. Our results demonstrate the feasibility of implementing a CD approach for developing a safe and effective LASV live-attenuated vaccine candidate. Moreover, rLASV-GPC/CD might provide investigators with a tool to safely study LASV outside maximum (biosafety level 4) containment, which could accelerate the elucidation of basic aspects of the molecular and cell biology of LASV and the development of novel LASV medical countermeasures.

Indexed as

A549 CellsAfrica, WesternAmino Acid SequenceAnimalsArenaviridaeArenavirusBunyaviridaeChlorocebus aethiopsCodonDisease Models, AnimalFemaleGenes, ViralGenome, ViralGlycoproteinsGuinea PigsHumansCodonGlycoproteinsRibavirinVaccines, AttenuatedViral VaccinesarenaviridArenaviridaearenavirusBunyaviralesbunyavirusguinea pigLassaLassa feverLassa virusLASVLAVlive-attenuated vaccinemammarenavirusstrain 13vaccineVHFviral hemorrhagic fever

Identifiers

PMID32098811
PMCPMC7042690
OpenAlexW3008257677

What OpenQuestion holds

Textmetadata
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.