About: Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants

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About: Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants Goto Sponge NotDistinct Permalink

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	Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants
Creator	Baric, Ralph Pickles, Raymond Whitmore, Alan Sims, Amy Yount, Boyd Donaldson, Eric Heise, Mark Curtis, Kristopher Davis, Nancy Deming, Damon Harkema, Jack Johnston, Robert Sheahan, Timothy Suthar, Mehul West, Ande Peiris, Joseph
Source	Medline; PMC
abstract	BACKGROUND: In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) was identified as the etiological agent of severe acute respiratory syndrome, a disease characterized by severe pneumonia that sometimes results in death. SARS-CoV is a zoonotic virus that crossed the species barrier, most likely originating from bats or from other species including civets, raccoon dogs, domestic cats, swine, and rodents. A SARS-CoV vaccine should confer long-term protection, especially in vulnerable senescent populations, against both the 2003 epidemic strains and zoonotic strains that may yet emerge from animal reservoirs. We report the comprehensive investigation of SARS vaccine efficacy in young and senescent mice following homologous and heterologous challenge. METHODS AND FINDINGS: Using Venezuelan equine encephalitis virus replicon particles (VRP) expressing the 2003 epidemic Urbani SARS-CoV strain spike (S) glycoprotein (VRP-S) or the nucleocapsid (N) protein from the same strain (VRP-N), we demonstrate that VRP-S, but not VRP-N vaccines provide complete short- and long-term protection against homologous strain challenge in young and senescent mice. To test VRP vaccine efficacy against a heterologous SARS-CoV, we used phylogenetic analyses, synthetic biology, and reverse genetics to construct a chimeric virus (icGDO3-S) encoding a synthetic S glycoprotein gene of the most genetically divergent human strain, GDO3, which clusters among the zoonotic SARS-CoV. icGD03-S replicated efficiently in human airway epithelial cells and in the lungs of young and senescent mice, and was highly resistant to neutralization with antisera directed against the Urbani strain. Although VRP-S vaccines provided complete short-term protection against heterologous icGD03-S challenge in young mice, only limited protection was seen in vaccinated senescent animals. VRP-N vaccines not only failed to protect from homologous or heterologous challenge, but resulted in enhanced immunopathology with eosinophilic infiltrates within the lungs of SARS-CoV–challenged mice. VRP-N–induced pathology presented at day 4, peaked around day 7, and persisted through day 14, and was likely mediated by cellular immune responses. CONCLUSIONS: This study identifies gaps and challenges in vaccine design for controlling future SARS-CoV zoonosis, especially in vulnerable elderly populations. The availability of a SARS-CoV virus bearing heterologous S glycoproteins provides a robust challenge inoculum for evaluating vaccine efficacy against zoonotic strains, the most likely source of future outbreaks.
has issue date	2006-12-26(xsd:dateTime)
bibo:doi	10.1371/journal.pmed.0030525
bibo:pmid	17194199
has license	cc-by
sha1sum (hex)	29b6131c0d572d383cbc6774b12e4471aa612b07
schema:url	https://doi.org/10.1371/journal.pmed.0030525
resource representing a document's title	Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants
has PubMed Central identifier	PMC1716185
has PubMed identifier	17194199
schema:publication	PLoS Med
resource representing a document's body	covid:29b6131c0d572d383cbc6774b12e4471aa612b07#body_text
is schema:about of	named entity 'RECOMBINANT' named entity 'Deming' named entity 'SPIKE' named entity 'EPIDEMIC' named entity 'ZOONOTIC' named entity 'MICE' named entity 'VACCINE EFFICACY' named entity 'EPIDEMIC' named entity 'SENESCENT' named entity 'BEARING' named entity 'ZOONOTIC' named entity 'SARS-COV' named entity 'VARIANTS' named entity 'SENESCENT' named entity 'RECOMBINANT' named entity 'SARS-COV' named entity 'BEARING' named entity 'CITATION' named entity 'DEMING' named entity 'MED' named entity 'DAVIS' named entity 'VACCINE EFFICACY' named entity 'VARIANTS' named entity 'SPIKE' named entity 'MICE' named entity 'zoonotic' named entity 'Heise' named entity 'senescent' named entity 'Senescent' named entity 'Epidemic' named entity 'lungs' named entity 'vaccine' named entity 'kDa' named entity 'RNA extraction' named entity 'vaccine' named entity 'EDTA' named entity 'death rate' named entity 'Lungs' named entity 'epitopes' named entity 'antibody' named entity 'biosafety level' named entity 'Fisher exact test' named entity 'polyclonal antibody' named entity 'long-term' named entity 'mouse model' named entity 'antisera' named entity 'Biotechnology' named entity 'UNC Chapel Hill' named entity 'phylogenetic analyses' named entity 'SARS-CoV' named entity 'vaccine' named entity 'plasmid' named entity 'epidemic' named entity 'senescent' named entity 'alveolitis' named entity 'antibody' named entity 'homologous' named entity 'kDa' named entity 'University of North Carolina' named entity 'amino acid' named entity 'young mice' named entity 'SARS-CoV' named entity 'mice' named entity 'vaccine strain' named entity 'senescent' named entity 'mice'

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