About: Immune Protection of Nonhuman Primates against Ebola Virus with Single Low-Dose Adenovirus Vectors Encoding Modified GPs

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An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Immune Protection of Nonhuman Primates against Ebola Virus with Single Low-Dose Adenovirus Vectors Encoding Modified GPs
Creator	Jahrling, Peter Roederer, Mario Goudsmit, Jaap Lamoreaux, Laurie Xu, Ling Yang, Zhi-Yong Sullivan, Nancy Custers, Jerome Geisbert, Joan Geisbert, Thomas Koup, Richard Nabel, Gary Shedlock, Devon Pau, Maria Popernack, Paul
Source	Medline; PMC
abstract	BACKGROUND: Ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. In the absence of effective therapies for Ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. Immunization with DNA and/or replication-defective adenoviral vectors (rAd) encoding the Ebola glycoprotein (GP) and nucleoprotein (NP) has been previously shown to confer specific protective immunity in nonhuman primates. GP can exert cytopathic effects on transfected cells in vitro, and multiple GP forms have been identified in nature, raising the question of which would be optimal for a human vaccine. METHODS AND FINDINGS: To address this question, we have explored the efficacy of mutant GPs from multiple Ebola virus strains with reduced in vitro cytopathicity and analyzed their protective effects in the primate challenge model, with or without NP. Deletion of the GP transmembrane domain eliminated in vitro cytopathicity but reduced its protective efficacy by at least one order of magnitude. In contrast, a point mutation was identified that abolished this cytopathicity but retained immunogenicity and conferred immune protection in the absence of NP. The minimal effective rAd dose was established at 10(10) particles, two logs lower than that used previously. CONCLUSIONS: Expression of specific GPs alone vectored by rAd are sufficient to confer protection against lethal challenge in a relevant nonhuman primate model. Elimination of NP from the vaccine and dose reductions to 10(10) rAd particles do not diminish protection and simplify the vaccine, providing the basis for selection of a human vaccine candidate.
has issue date	2006-05-16(xsd:dateTime)
bibo:doi	10.1371/journal.pmed.0030177
bibo:pmid	16683867
has license	cc0
sha1sum (hex)	f38f3b112e4b702b60ba56be806d418bbb2b83c3
schema:url	https://doi.org/10.1371/journal.pmed.0030177
resource representing a document's title	Immune Protection of Nonhuman Primates against Ebola Virus with Single Low-Dose Adenovirus Vectors Encoding Modified GPs
has PubMed Central identifier	PMC1459482
has PubMed identifier	16683867
schema:publication	PLoS Med
resource representing a document's body	covid:f38f3b112e4b702b60ba56be806d418bbb2b83c3#body_text
is schema:about of	named entity 'INTELLECTUAL PROPERTY' named entity 'BASED' named entity 'GENE' named entity 'COMPANY' named entity 'Ebola vaccine' named entity 'Immune' named entity 'vaccines' named entity 'EBOLA VIRUS' named entity 'IMMUNE PROTECTION' named entity 'VECTORS' named entity 'VACCINE' named entity 'INTERESTS' named entity 'DEVELOPING' named entity 'GPS' named entity 'ADENOVIRUS' named entity 'LOW-DOSE' named entity 'SINGLE' named entity 'NJS' named entity 'EBOLA' named entity 'VACCINES' named entity 'ENCODING' named entity 'MODIFIED' named entity 'NONHUMAN PRIMATES' named entity 'Modified' named entity 'Primates' named entity 'vaccines' named entity 'antigen' named entity 'TNF-a' named entity 'adenoviral' named entity 'horseradish peroxidase' named entity 'cytokine' named entity 'Ebola' named entity 'DTM' named entity 'protein' named entity 'Ebola' named entity 'virus' named entity 'Ebola' named entity 'Ebola' named entity 'immune responses' named entity 'immune response' named entity 'amino acid' named entity 'Zaire' named entity 'lymphocytes' named entity 'cellular expression' named entity 'Ebola' named entity 'virus replication' named entity 'CD4' named entity 'Ebola' named entity 'protein' named entity 'protein' named entity 'nucleoprotein' named entity 'genome' named entity 'HEK293' named entity 'clinical trials' named entity 'Sudan' named entity 'Zaire strain' named entity 'transfected' named entity 'IgG' named entity 'immunogens' named entity 'anion-exchange' named entity 'correlation' named entity 'TNF-a' named entity 'CD28' named entity 'HUVECs' named entity 'FACS' named entity 'Crucell' named entity 'transcriptional control'

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