SrasV1, PascalFrancis, Corpus, bibRecord, 000079

A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon Challenge

Identifieur interne : 000079 ( PascalFrancis/Corpus ); précédent : 000078; suivant : 000080

A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon Challenge

Auteurs : Meagan Bolles ; Damon Deming ; Kristin Long ; Sudhakar Agnihothram ; Alan Whitmore ; Martin Ferris ; William Funkhouser ; Lisa Gralinski ; Allison Totura ; Mark Heise ; Ralph S. Baric

Source :

Journal of virology [ 0022-538X ] ; 2011.

RBID : Pascal:12-0013548

Descripteurs français

Pascal (Inist)
- Coronavirus, Souris, Vaccin, Syndrome respiratoire aigu sévère.

English descriptors

KwdEn :
- Coronavirus, Mouse, Severe acute respiratory syndrome, Vaccine.

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) is an important emerging virus that is highly pathogenic in aged populations and is maintained with great diversity in zoonotic reservoirs. While a variety of vaccine platforms have shown efficacy in young-animal models and against homologous viral strains, vaccine efficacy has not been thoroughly evaluated using highly pathogenic variants that replicate the acute end stage lung disease phenotypes seen during the human epidemic. Using an adjuvanted and an unadjuvanted double-inactivated SARS-CoV (DIV) vaccine, we demonstrate an eosinophilic immunopathology in aged mice comparable to that seen in mice immunized with the SARS nucleocapsid protein, and poor protection against a nonlethal heterologous challenge. In young and 1-year-old animals, we demonstrate that adjuvanted DIV vaccine provides protection against lethal disease in young animals following homologous and heterologous challenge, although enhanced immune pathology and eosinophilia are evident following heterologous challenge. In the absence of alum, DIV vaccine performed poorly in young animals challenged with lethal homologous or heterologous strains. In contrast, DIV vaccines (both adjuvanted and unadjuvanted) performed poorly in aged-animal models. Importantly, aged animals displayed increased eosinophilic immune pathology in the lungs and were not protected against significant virus replication. These data raise significant concerns regarding DIV vaccine safety and highlight the need for additional studies of the molecular mechanisms governing DIV-induced eosinophilia and vaccine failure, especially in the more vulnerable aged-animal models of human disease.

Notice en format standard (ISO 2709)

Pour connaître la documentation sur le format Inist Standard.

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A11	`02`	`1`		`@1 DEMING (Damon)`
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A11	`05`	`1`		`@1 WHITMORE (Alan)`
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A11	`07`	`1`		`@1 FUNKHOUSER (William)`
A11	`08`	`1`		`@1 GRALINSKI (Lisa)`
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A11	`10`	`1`		`@1 HEISE (Mark)`
A11	`11`	`1`		`@1 BARIC (Ralph S.)`
A14	`01`			`@1 Department of Microbiology and Immunology, University of North Carolina at Chapel Hill @2 Chapel Hill, North Carolina @3 USA @Z 1 aut. @Z 2 aut. @Z 9 aut. @Z 10 aut. @Z 11 aut.`
A14	`02`			`@1 Carolina Vaccine Institute, University of North Carolina at Chapel Hill @2 Chapel Hill, North Carolina @3 USA @Z 3 aut. @Z 5 aut. @Z 6 aut. @Z 10 aut.`
A14	`03`			`@1 Department of Epidemiology, University of North Carolina at Chapel Hill @2 Chapel Hill, North Carolina @3 USA @Z 4 aut. @Z 8 aut. @Z 11 aut.`
A14	`04`			`@1 Department of Pathology, University of North Carolina School of Medicine @2 Chapel Hill, North Carolina @3 USA @Z 7 aut.`
A14	`05`			`@1 Department of Genetics, University of North Carolina at Chapel Hill @2 Chapel Hill, North Carolina @3 USA @Z 10 aut.`
A20				`@1 12201-12215`
A21				`@1 2011`
A23	`01`			`@0 ENG`
A43	`01`			`@1 INIST @2 13592 @5 354000507305310100`
A44				`@0 0000 @1 © 2012 INIST-CNRS. All rights reserved.`
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C01	`01`		`ENG`	@0 Severe acute respiratory syndrome coronavirus (SARS-CoV) is an important emerging virus that is highly pathogenic in aged populations and is maintained with great diversity in zoonotic reservoirs. While a variety of vaccine platforms have shown efficacy in young-animal models and against homologous viral strains, vaccine efficacy has not been thoroughly evaluated using highly pathogenic variants that replicate the acute end stage lung disease phenotypes seen during the human epidemic. Using an adjuvanted and an unadjuvanted double-inactivated SARS-CoV (DIV) vaccine, we demonstrate an eosinophilic immunopathology in aged mice comparable to that seen in mice immunized with the SARS nucleocapsid protein, and poor protection against a nonlethal heterologous challenge. In young and 1-year-old animals, we demonstrate that adjuvanted DIV vaccine provides protection against lethal disease in young animals following homologous and heterologous challenge, although enhanced immune pathology and eosinophilia are evident following heterologous challenge. In the absence of alum, DIV vaccine performed poorly in young animals challenged with lethal homologous or heterologous strains. In contrast, DIV vaccines (both adjuvanted and unadjuvanted) performed poorly in aged-animal models. Importantly, aged animals displayed increased eosinophilic immune pathology in the lungs and were not protected against significant virus replication. These data raise significant concerns regarding DIV vaccine safety and highlight the need for additional studies of the molecular mechanisms governing DIV-induced eosinophilia and vaccine failure, especially in the more vulnerable aged-animal models of human disease.
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C03	`01`	`X`	`SPA`	`@0 Coronavirus @2 NW @5 01`
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C03	`02`	`X`	`ENG`	`@0 Mouse @5 02`
C03	`02`	`X`	`SPA`	`@0 Ratón @5 02`
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C07	`04`	`X`	`SPA`	`@0 Rodentia @2 NS`
C07	`05`	`X`	`FRE`	`@0 Mammalia @2 NS`
C07	`05`	`X`	`ENG`	`@0 Mammalia @2 NS`
C07	`05`	`X`	`SPA`	`@0 Mammalia @2 NS`
C07	`06`	`X`	`FRE`	`@0 Vertebrata @2 NS`
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C07	`08`	`X`	`FRE`	`@0 Virose`
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C07	`10`	`X`	`FRE`	`@0 Pathologie des poumons @5 16`
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C07	`10`	`X`	`SPA`	`@0 Pulmón patología @5 16`
N21				`@1 002`
N44	`01`			`@1 OTO`
N82				`@1 OTO`

Format Inist (serveur)

NO :	PASCAL 12-0013548 INIST
ET :	A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon Challenge
AU :	BOLLES (Meagan); DEMING (Damon); LONG (Kristin); AGNIHOTHRAM (Sudhakar); WHITMORE (Alan); FERRIS (Martin); FUNKHOUSER (William); GRALINSKI (Lisa); TOTURA (Allison); HEISE (Mark); BARIC (Ralph S.)
AF :	Department of Microbiology and Immunology, University of North Carolina at Chapel Hill/Chapel Hill, North Carolina/Etats-Unis (1 aut., 2 aut., 9 aut., 10 aut., 11 aut.); Carolina Vaccine Institute, University of North Carolina at Chapel Hill/Chapel Hill, North Carolina/Etats-Unis (3 aut., 5 aut., 6 aut., 10 aut.); Department of Epidemiology, University of North Carolina at Chapel Hill/Chapel Hill, North Carolina/Etats-Unis (4 aut., 8 aut., 11 aut.); Department of Pathology, University of North Carolina School of Medicine/Chapel Hill, North Carolina/Etats-Unis (7 aut.); Department of Genetics, University of North Carolina at Chapel Hill/Chapel Hill, North Carolina/Etats-Unis (10 aut.)
DT :	Publication en série; Niveau analytique
SO :	Journal of virology; ISSN 0022-538X; Etats-Unis; Da. 2011; Vol. 85; No. 23; Pp. 12201-12215; Bibl. 67 ref.
LA :	Anglais
EA :	Severe acute respiratory syndrome coronavirus (SARS-CoV) is an important emerging virus that is highly pathogenic in aged populations and is maintained with great diversity in zoonotic reservoirs. While a variety of vaccine platforms have shown efficacy in young-animal models and against homologous viral strains, vaccine efficacy has not been thoroughly evaluated using highly pathogenic variants that replicate the acute end stage lung disease phenotypes seen during the human epidemic. Using an adjuvanted and an unadjuvanted double-inactivated SARS-CoV (DIV) vaccine, we demonstrate an eosinophilic immunopathology in aged mice comparable to that seen in mice immunized with the SARS nucleocapsid protein, and poor protection against a nonlethal heterologous challenge. In young and 1-year-old animals, we demonstrate that adjuvanted DIV vaccine provides protection against lethal disease in young animals following homologous and heterologous challenge, although enhanced immune pathology and eosinophilia are evident following heterologous challenge. In the absence of alum, DIV vaccine performed poorly in young animals challenged with lethal homologous or heterologous strains. In contrast, DIV vaccines (both adjuvanted and unadjuvanted) performed poorly in aged-animal models. Importantly, aged animals displayed increased eosinophilic immune pathology in the lungs and were not protected against significant virus replication. These data raise significant concerns regarding DIV vaccine safety and highlight the need for additional studies of the molecular mechanisms governing DIV-induced eosinophilia and vaccine failure, especially in the more vulnerable aged-animal models of human disease.
CC :	002A05C10; 002A05C07
FD :	Coronavirus; Souris; Vaccin; Syndrome respiratoire aigu sévère
FG :	Coronaviridae; Nidovirales; Virus; Rodentia; Mammalia; Vertebrata; Pathologie de l'appareil respiratoire; Virose; Infection; Pathologie des poumons
ED :	Coronavirus; Mouse; Vaccine; Severe acute respiratory syndrome
EG :	Coronaviridae; Nidovirales; Virus; Rodentia; Mammalia; Vertebrata; Respiratory disease; Viral disease; Infection; Lung disease
SD :	Coronavirus; Ratón; Vacuna; Síndrome respiratorio agudo severo
LO :	INIST-13592.354000507305310100
ID :	12-0013548

Links to Exploration step

Pascal:12-0013548

Le document en format XML

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<author><name sortKey="Heise, Mark" sort="Heise, Mark" uniqKey="Heise M" first="Mark" last="Heise">Mark Heise</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon Challenge</title>
<author><name sortKey="Bolles, Meagan" sort="Bolles, Meagan" uniqKey="Bolles M" first="Meagan" last="Bolles">Meagan Bolles</name>
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<author><name sortKey="Deming, Damon" sort="Deming, Damon" uniqKey="Deming D" first="Damon" last="Deming">Damon Deming</name>
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<author><name sortKey="Long, Kristin" sort="Long, Kristin" uniqKey="Long K" first="Kristin" last="Long">Kristin Long</name>
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<author><name sortKey="Agnihothram, Sudhakar" sort="Agnihothram, Sudhakar" uniqKey="Agnihothram S" first="Sudhakar" last="Agnihothram">Sudhakar Agnihothram</name>
<affiliation><inist:fA14 i1="03"><s1>Department of Epidemiology, University of North Carolina at Chapel Hill</s1>
<s2>Chapel Hill, North Carolina</s2>
<s3>USA</s3>
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</author>
<author><name sortKey="Whitmore, Alan" sort="Whitmore, Alan" uniqKey="Whitmore A" first="Alan" last="Whitmore">Alan Whitmore</name>
<affiliation><inist:fA14 i1="02"><s1>Carolina Vaccine Institute, University of North Carolina at Chapel Hill</s1>
<s2>Chapel Hill, North Carolina</s2>
<s3>USA</s3>
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<author><name sortKey="Ferris, Martin" sort="Ferris, Martin" uniqKey="Ferris M" first="Martin" last="Ferris">Martin Ferris</name>
<affiliation><inist:fA14 i1="02"><s1>Carolina Vaccine Institute, University of North Carolina at Chapel Hill</s1>
<s2>Chapel Hill, North Carolina</s2>
<s3>USA</s3>
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<author><name sortKey="Funkhouser, William" sort="Funkhouser, William" uniqKey="Funkhouser W" first="William" last="Funkhouser">William Funkhouser</name>
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<s2>Chapel Hill, North Carolina</s2>
<s3>USA</s3>
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</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Gralinski, Lisa" sort="Gralinski, Lisa" uniqKey="Gralinski L" first="Lisa" last="Gralinski">Lisa Gralinski</name>
<affiliation><inist:fA14 i1="03"><s1>Department of Epidemiology, University of North Carolina at Chapel Hill</s1>
<s2>Chapel Hill, North Carolina</s2>
<s3>USA</s3>
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<author><name sortKey="Totura, Allison" sort="Totura, Allison" uniqKey="Totura A" first="Allison" last="Totura">Allison Totura</name>
<affiliation><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill</s1>
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<front><div type="abstract" xml:lang="en">Severe acute respiratory syndrome coronavirus (SARS-CoV) is an important emerging virus that is highly pathogenic in aged populations and is maintained with great diversity in zoonotic reservoirs. While a variety of vaccine platforms have shown efficacy in young-animal models and against homologous viral strains, vaccine efficacy has not been thoroughly evaluated using highly pathogenic variants that replicate the acute end stage lung disease phenotypes seen during the human epidemic. Using an adjuvanted and an unadjuvanted double-inactivated SARS-CoV (DIV) vaccine, we demonstrate an eosinophilic immunopathology in aged mice comparable to that seen in mice immunized with the SARS nucleocapsid protein, and poor protection against a nonlethal heterologous challenge. In young and 1-year-old animals, we demonstrate that adjuvanted DIV vaccine provides protection against lethal disease in young animals following homologous and heterologous challenge, although enhanced immune pathology and eosinophilia are evident following heterologous challenge. In the absence of alum, DIV vaccine performed poorly in young animals challenged with lethal homologous or heterologous strains. In contrast, DIV vaccines (both adjuvanted and unadjuvanted) performed poorly in aged-animal models. Importantly, aged animals displayed increased eosinophilic immune pathology in the lungs and were not protected against significant virus replication. These data raise significant concerns regarding DIV vaccine safety and highlight the need for additional studies of the molecular mechanisms governing DIV-induced eosinophilia and vaccine failure, especially in the more vulnerable aged-animal models of human disease.</div>
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<ET>A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon Challenge</ET>
<AU>BOLLES (Meagan); DEMING (Damon); LONG (Kristin); AGNIHOTHRAM (Sudhakar); WHITMORE (Alan); FERRIS (Martin); FUNKHOUSER (William); GRALINSKI (Lisa); TOTURA (Allison); HEISE (Mark); BARIC (Ralph S.)</AU>
<AF>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill/Chapel Hill, North Carolina/Etats-Unis (1 aut., 2 aut., 9 aut., 10 aut., 11 aut.); Carolina Vaccine Institute, University of North Carolina at Chapel Hill/Chapel Hill, North Carolina/Etats-Unis (3 aut., 5 aut., 6 aut., 10 aut.); Department of Epidemiology, University of North Carolina at Chapel Hill/Chapel Hill, North Carolina/Etats-Unis (4 aut., 8 aut., 11 aut.); Department of Pathology, University of North Carolina School of Medicine/Chapel Hill, North Carolina/Etats-Unis (7 aut.); Department of Genetics, University of North Carolina at Chapel Hill/Chapel Hill, North Carolina/Etats-Unis (10 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
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A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon Challenge

A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon Challenge

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