Successful Vaccination Strategies That Protect Aged Mice from Lethal Challenge from Influenza Virus and Heterologous Severe Acute Respiratory Syndrome Coronavirus
Identifieur interne : 000119 ( PascalFrancis/Corpus ); précédent : 000118; suivant : 000120Successful Vaccination Strategies That Protect Aged Mice from Lethal Challenge from Influenza Virus and Heterologous Severe Acute Respiratory Syndrome Coronavirus
Auteurs : Timothy Sheahan ; Alan Whitmore ; Kristin Long ; Martin Ferris ; Barry Rockx ; William Funkhouser ; Eric Donaldson ; Lisa Gralinski ; Martha Collier ; Mark Heise ; Nancy Davis ; Robert Johnston ; Ralph S. BaricSource :
- Journal of virology [ 0022-538X ] ; 2011.
Descripteurs français
- Pascal (Inist)
English descriptors
Abstract
Newly emerging viruses often circulate as a heterogeneous swarm in wild animal reservoirs prior to their emergence in humans, and their antigenic identities are often unknown until an outbreak situation. The newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV) and reemerging influenza virus cause disproportionate disease in the aged, who are also notoriously difficult to successfully vaccinate, likely due to immunosenescence. To protect against future emerging strains, vaccine platforms should induce broad cross-reactive immunity that is sufficient to protect from homologous and heterologous challenge in all ages. From initial studies, we hypothesized that attenuated Venezuelan equine encephalitis virus (VEE) replicon particle (VRP) vaccine glycoproteins mediated vaccine failure in the aged. We then compared the efficacies of vaccines bearing attenuated (VRP3014) or wild-type VEE glycoproteins (VRP3000) in young and aged mice within novel models of severe SARS-CoV pathogenesis. Aged animals receiving VRP3000-based vaccines were protected from SARS-CoV disease, while animals receiving the VRP3014-based vaccines were not. The superior protection for the aged observed with VRP3000-based vaccines was confirmed in a lethal influenza virus challenge model. While the VRP3000 vaccine's immune responses in the aged were sufficient to protect against lethal homologous and heterologous challenge, our data suggest that innate defects within the VRP3014 platform mediate vaccine failure. Exploration into the mechanism(s) of successful vaccination in the immunosenescent should aid in the development of successful vaccine strategies for other viral diseases disproportionately affecting the elderly, like West Nile virus, influenza virus, norovirus, or other emerging viruses of the future.
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Format Inist (serveur)
| NO : | PASCAL 11-0091204 INIST |
|---|---|
| ET : | Successful Vaccination Strategies That Protect Aged Mice from Lethal Challenge from Influenza Virus and Heterologous Severe Acute Respiratory Syndrome Coronavirus |
| AU : | SHEAHAN (Timothy); WHITMORE (Alan); LONG (Kristin); FERRIS (Martin); ROCKX (Barry); FUNKHOUSER (William); DONALDSON (Eric); GRALINSKI (Lisa); COLLIER (Martha); HEISE (Mark); DAVIS (Nancy); JOHNSTON (Robert); BARIC (Ralph S.) |
| AF : | Department of Microbiology and Immunology, University of North Carolina at Chapel Hill/Chapel Hill, North Carolina/Etats-Unis (1 aut., 10 aut., 11 aut., 12 aut., 13 aut.); Carolina Vaccine Institute, University of North Carolina at Chapel Hill/Chapel Hill, North Carolina/Etats-Unis (2 aut., 3 aut., 4 aut., 9 aut., 10 aut., 11 aut., 12 aut.); Department of Epidemiology, University of North Carolina at Chapel Hill/Chapel Hill, North Carolina/Etats-Unis (1 aut., 5 aut., 7 aut., 8 aut., 13 aut.); Department of Pathology, University of North Carolina School of Medicine/Chapel Hill, North Carolina/Etats-Unis (6 aut.); Department of Genetics, University of North Carolina at Chapel Hill/Chapel Hill, North Carolina/Etats-Unis (10 aut.); Laboratory of hirology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health/Hamilton, Montana/Etats-Unis (5 aut.) |
| DT : | Publication en série; Niveau analytique |
| SO : | Journal of virology; ISSN 0022-538X; Etats-Unis; Da. 2011; Vol. 85; No. 1; Pp. 217-230; Bibl. 70 ref. |
| LA : | Anglais |
| EA : | Newly emerging viruses often circulate as a heterogeneous swarm in wild animal reservoirs prior to their emergence in humans, and their antigenic identities are often unknown until an outbreak situation. The newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV) and reemerging influenza virus cause disproportionate disease in the aged, who are also notoriously difficult to successfully vaccinate, likely due to immunosenescence. To protect against future emerging strains, vaccine platforms should induce broad cross-reactive immunity that is sufficient to protect from homologous and heterologous challenge in all ages. From initial studies, we hypothesized that attenuated Venezuelan equine encephalitis virus (VEE) replicon particle (VRP) vaccine glycoproteins mediated vaccine failure in the aged. We then compared the efficacies of vaccines bearing attenuated (VRP3014) or wild-type VEE glycoproteins (VRP3000) in young and aged mice within novel models of severe SARS-CoV pathogenesis. Aged animals receiving VRP3000-based vaccines were protected from SARS-CoV disease, while animals receiving the VRP3014-based vaccines were not. The superior protection for the aged observed with VRP3000-based vaccines was confirmed in a lethal influenza virus challenge model. While the VRP3000 vaccine's immune responses in the aged were sufficient to protect against lethal homologous and heterologous challenge, our data suggest that innate defects within the VRP3014 platform mediate vaccine failure. Exploration into the mechanism(s) of successful vaccination in the immunosenescent should aid in the development of successful vaccine strategies for other viral diseases disproportionately affecting the elderly, like West Nile virus, influenza virus, norovirus, or other emerging viruses of the future. |
| CC : | 002A05C10 |
| FD : | Souris; Influenzavirus; Coronavirus; Vaccination; Syndrome respiratoire aigu sévère |
| FG : | Rodentia; Mammalia; Vertebrata; Orthomyxoviridae; Virus; Coronaviridae; Nidovirales; Pathologie de l'appareil respiratoire; Virose; Infection; Pathologie des poumons |
| ED : | Mouse; Influenzavirus; Coronavirus; Vaccination; Severe acute respiratory syndrome |
| EG : | Rodentia; Mammalia; Vertebrata; Orthomyxoviridae; Virus; Coronaviridae; Nidovirales; Respiratory disease; Viral disease; Infection; Lung disease |
| SD : | Ratón; Influenzavirus; Coronavirus; Vacunación; Síndrome respiratorio agudo severo |
| LO : | INIST-13592.354000191891830190 |
| ID : | 11-0091204 |
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Pascal:11-0091204Le document en format XML
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last="Baric">Ralph S. Baric</name><affiliation><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation><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><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">11-0091204</idno><date when="2011">2011</date><idno type="stanalyst">PASCAL 11-0091204 INIST</idno><idno type="RBID">Pascal:11-0091204</idno><idno type="wicri:Area/PascalFrancis/Corpus">000119</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Successful Vaccination Strategies That Protect Aged Mice from Lethal Challenge from Influenza Virus and Heterologous Severe Acute Respiratory Syndrome Coronavirus</title><author><name sortKey="Sheahan, Timothy" sort="Sheahan, Timothy" uniqKey="Sheahan T" first="Timothy" last="Sheahan">Timothy Sheahan</name><affiliation><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation><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><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></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><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Long, Kristin" sort="Long, Kristin" uniqKey="Long K" first="Kristin" last="Long">Kristin Long</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><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14></affiliation></author><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><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Rockx, Barry" sort="Rockx, Barry" uniqKey="Rockx B" first="Barry" last="Rockx">Barry Rockx</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><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="06"><s1>Laboratory of hirology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Hamilton, Montana</s2><s3>USA</s3><sZ>5 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Funkhouser, William" sort="Funkhouser, William" uniqKey="Funkhouser W" first="William" last="Funkhouser">William Funkhouser</name><affiliation><inist:fA14 i1="04"><s1>Department of Pathology, University of North Carolina School of Medicine</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>6 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Donaldson, Eric" sort="Donaldson, Eric" uniqKey="Donaldson E" first="Eric" last="Donaldson">Eric Donaldson</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><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>13 aut.</sZ></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><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Collier, Martha" sort="Collier, Martha" uniqKey="Collier M" first="Martha" last="Collier">Martha Collier</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><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Heise, Mark" sort="Heise, Mark" uniqKey="Heise M" first="Mark" last="Heise">Mark Heise</name><affiliation><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation><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><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14></affiliation><affiliation><inist:fA14 i1="05"><s1>Department of Genetics, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>10 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Davis, Nancy" sort="Davis, Nancy" uniqKey="Davis N" first="Nancy" last="Davis">Nancy Davis</name><affiliation><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation><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><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Johnston, Robert" sort="Johnston, Robert" uniqKey="Johnston R" first="Robert" last="Johnston">Robert Johnston</name><affiliation><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation><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><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><affiliation><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation><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><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></author></analytic><series><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Coronavirus</term><term>Influenzavirus</term><term>Mouse</term><term>Severe acute respiratory syndrome</term><term>Vaccination</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Souris</term><term>Influenzavirus</term><term>Coronavirus</term><term>Vaccination</term><term>Syndrome respiratoire aigu sévère</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Newly emerging viruses often circulate as a heterogeneous swarm in wild animal reservoirs prior to their emergence in humans, and their antigenic identities are often unknown until an outbreak situation. The newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV) and reemerging influenza virus cause disproportionate disease in the aged, who are also notoriously difficult to successfully vaccinate, likely due to immunosenescence. To protect against future emerging strains, vaccine platforms should induce broad cross-reactive immunity that is sufficient to protect from homologous and heterologous challenge in all ages. From initial studies, we hypothesized that attenuated Venezuelan equine encephalitis virus (VEE) replicon particle (VRP) vaccine glycoproteins mediated vaccine failure in the aged. We then compared the efficacies of vaccines bearing attenuated (VRP<sub>3014</sub>) or wild-type VEE glycoproteins (VRP<sub>3000</sub>) in young and aged mice within novel models of severe SARS-CoV pathogenesis. Aged animals receiving VRP<sub>3000</sub>-based vaccines were protected from SARS-CoV disease, while animals receiving the VRP<sub>3014</sub>-based vaccines were not. The superior protection for the aged observed with VRP<sub>3000</sub>-based vaccines was confirmed in a lethal influenza virus challenge model. While the VRP<sub>3000</sub> vaccine's immune responses in the aged were sufficient to protect against lethal homologous and heterologous challenge, our data suggest that innate defects within the VRP<sub>3014</sub> platform mediate vaccine failure. Exploration into the mechanism(s) of successful vaccination in the immunosenescent should aid in the development of successful vaccine strategies for other viral diseases disproportionately affecting the elderly, like West Nile virus, influenza virus, norovirus, or other emerging viruses of the future.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0022-538X</s0></fA01><fA03 i2="1"><s0>J. virol.</s0></fA03><fA05><s2>85</s2></fA05><fA06><s2>1</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Successful Vaccination Strategies That Protect Aged Mice from Lethal Challenge from Influenza Virus and Heterologous Severe Acute Respiratory Syndrome Coronavirus</s1></fA08><fA11 i1="01" i2="1"><s1>SHEAHAN (Timothy)</s1></fA11><fA11 i1="02" i2="1"><s1>WHITMORE (Alan)</s1></fA11><fA11 i1="03" i2="1"><s1>LONG (Kristin)</s1></fA11><fA11 i1="04" i2="1"><s1>FERRIS (Martin)</s1></fA11><fA11 i1="05" i2="1"><s1>ROCKX (Barry)</s1></fA11><fA11 i1="06" i2="1"><s1>FUNKHOUSER (William)</s1></fA11><fA11 i1="07" i2="1"><s1>DONALDSON (Eric)</s1></fA11><fA11 i1="08" i2="1"><s1>GRALINSKI (Lisa)</s1></fA11><fA11 i1="09" i2="1"><s1>COLLIER (Martha)</s1></fA11><fA11 i1="10" i2="1"><s1>HEISE (Mark)</s1></fA11><fA11 i1="11" i2="1"><s1>DAVIS (Nancy)</s1></fA11><fA11 i1="12" i2="1"><s1>JOHNSTON (Robert)</s1></fA11><fA11 i1="13" i2="1"><s1>BARIC (Ralph S.)</s1></fA11><fA14 i1="01"><s1>Department of Microbiology and Immunology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></fA14><fA14 i1="02"><s1>Carolina Vaccine Institute, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ></fA14><fA14 i1="03"><s1>Department of Epidemiology, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>13 aut.</sZ></fA14><fA14 i1="04"><s1>Department of Pathology, University of North Carolina School of Medicine</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>6 aut.</sZ></fA14><fA14 i1="05"><s1>Department of Genetics, University of North Carolina at Chapel Hill</s1><s2>Chapel Hill, North Carolina</s2><s3>USA</s3><sZ>10 aut.</sZ></fA14><fA14 i1="06"><s1>Laboratory of hirology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health</s1><s2>Hamilton, Montana</s2><s3>USA</s3><sZ>5 aut.</sZ></fA14><fA20><s1>217-230</s1></fA20><fA21><s1>2011</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>13592</s2><s5>354000191891830190</s5></fA43><fA44><s0>0000</s0><s1>© 2011 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>70 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>11-0091204</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Journal of virology</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>Newly emerging viruses often circulate as a heterogeneous swarm in wild animal reservoirs prior to their emergence in humans, and their antigenic identities are often unknown until an outbreak situation. The newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV) and reemerging influenza virus cause disproportionate disease in the aged, who are also notoriously difficult to successfully vaccinate, likely due to immunosenescence. To protect against future emerging strains, vaccine platforms should induce broad cross-reactive immunity that is sufficient to protect from homologous and heterologous challenge in all ages. From initial studies, we hypothesized that attenuated Venezuelan equine encephalitis virus (VEE) replicon particle (VRP) vaccine glycoproteins mediated vaccine failure in the aged. We then compared the efficacies of vaccines bearing attenuated (VRP<sub>3014</sub>) or wild-type VEE glycoproteins (VRP<sub>3000</sub>) in young and aged mice within novel models of severe SARS-CoV pathogenesis. Aged animals receiving VRP<sub>3000</sub>-based vaccines were protected from SARS-CoV disease, while animals receiving the VRP<sub>3014</sub>-based vaccines were not. The superior protection for the aged observed with VRP<sub>3000</sub>-based vaccines was confirmed in a lethal influenza virus challenge model. While the VRP<sub>3000</sub> vaccine's immune responses in the aged were sufficient to protect against lethal homologous and heterologous challenge, our data suggest that innate defects within the VRP<sub>3014</sub> platform mediate vaccine failure. Exploration into the mechanism(s) of successful vaccination in the immunosenescent should aid in the development of successful vaccine strategies for other viral diseases disproportionately affecting the elderly, like West Nile virus, influenza virus, norovirus, or other emerging viruses of the future.</s0></fC01><fC02 i1="01" i2="X"><s0>002A05C10</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Souris</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Mouse</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Ratón</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Influenzavirus</s0><s2>NW</s2><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Influenzavirus</s0><s2>NW</s2><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Influenzavirus</s0><s2>NW</s2><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Coronavirus</s0><s2>NW</s2><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Coronavirus</s0><s2>NW</s2><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Coronavirus</s0><s2>NW</s2><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Vaccination</s0><s5>05</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Vaccination</s0><s5>05</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Vacunación</s0><s5>05</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Syndrome respiratoire aigu sévère</s0><s2>NM</s2><s5>14</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Severe acute respiratory syndrome</s0><s2>NM</s2><s5>14</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Síndrome respiratorio agudo severo</s0><s2>NM</s2><s5>14</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Rodentia</s0><s2>NS</s2></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Rodentia</s0><s2>NS</s2></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Rodentia</s0><s2>NS</s2></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Orthomyxoviridae</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Orthomyxoviridae</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Orthomyxoviridae</s0><s2>NW</s2></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="07" i2="X" l="FRE"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="07" i2="X" l="ENG"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="07" i2="X" l="SPA"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="08" i2="X" l="FRE"><s0>Pathologie de l'appareil respiratoire</s0><s5>13</s5></fC07><fC07 i1="08" i2="X" l="ENG"><s0>Respiratory disease</s0><s5>13</s5></fC07><fC07 i1="08" i2="X" l="SPA"><s0>Aparato respiratorio patología</s0><s5>13</s5></fC07><fC07 i1="09" i2="X" l="FRE"><s0>Virose</s0></fC07><fC07 i1="09" i2="X" l="ENG"><s0>Viral disease</s0></fC07><fC07 i1="09" i2="X" l="SPA"><s0>Virosis</s0></fC07><fC07 i1="10" i2="X" l="FRE"><s0>Infection</s0></fC07><fC07 i1="10" i2="X" l="ENG"><s0>Infection</s0></fC07><fC07 i1="10" i2="X" l="SPA"><s0>Infección</s0></fC07><fC07 i1="11" i2="X" l="FRE"><s0>Pathologie des poumons</s0><s5>16</s5></fC07><fC07 i1="11" i2="X" l="ENG"><s0>Lung disease</s0><s5>16</s5></fC07><fC07 i1="11" i2="X" l="SPA"><s0>Pulmón patología</s0><s5>16</s5></fC07><fN21><s1>059</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard><server><NO>PASCAL 11-0091204 INIST</NO><ET>Successful Vaccination Strategies That Protect Aged Mice from Lethal Challenge from Influenza Virus and Heterologous Severe Acute Respiratory Syndrome Coronavirus</ET><AU>SHEAHAN (Timothy); WHITMORE (Alan); LONG (Kristin); FERRIS (Martin); ROCKX (Barry); FUNKHOUSER (William); DONALDSON (Eric); GRALINSKI (Lisa); COLLIER (Martha); HEISE (Mark); DAVIS (Nancy); JOHNSTON (Robert); 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., 10 aut., 11 aut., 12 aut., 13 aut.); Carolina Vaccine Institute, University of North Carolina at Chapel Hill/Chapel Hill, North Carolina/Etats-Unis (2 aut., 3 aut., 4 aut., 9 aut., 10 aut., 11 aut., 12 aut.); Department of Epidemiology, University of North Carolina at Chapel Hill/Chapel Hill, North Carolina/Etats-Unis (1 aut., 5 aut., 7 aut., 8 aut., 13 aut.); Department of Pathology, University of North Carolina School of Medicine/Chapel Hill, North Carolina/Etats-Unis (6 aut.); Department of Genetics, University of North Carolina at Chapel Hill/Chapel Hill, North Carolina/Etats-Unis (10 aut.); Laboratory of hirology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health/Hamilton, Montana/Etats-Unis (5 aut.)</AF><DT>Publication en série; Niveau analytique</DT><SO>Journal of virology; ISSN 0022-538X; Etats-Unis; Da. 2011; Vol. 85; No. 1; Pp. 217-230; Bibl. 70 ref.</SO><LA>Anglais</LA><EA>Newly emerging viruses often circulate as a heterogeneous swarm in wild animal reservoirs prior to their emergence in humans, and their antigenic identities are often unknown until an outbreak situation. The newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV) and reemerging influenza virus cause disproportionate disease in the aged, who are also notoriously difficult to successfully vaccinate, likely due to immunosenescence. To protect against future emerging strains, vaccine platforms should induce broad cross-reactive immunity that is sufficient to protect from homologous and heterologous challenge in all ages. From initial studies, we hypothesized that attenuated Venezuelan equine encephalitis virus (VEE) replicon particle (VRP) vaccine glycoproteins mediated vaccine failure in the aged. We then compared the efficacies of vaccines bearing attenuated (VRP<sub>3014</sub>) or wild-type VEE glycoproteins (VRP<sub>3000</sub>) in young and aged mice within novel models of severe SARS-CoV pathogenesis. Aged animals receiving VRP<sub>3000</sub>-based vaccines were protected from SARS-CoV disease, while animals receiving the VRP<sub>3014</sub>-based vaccines were not. The superior protection for the aged observed with VRP<sub>3000</sub>-based vaccines was confirmed in a lethal influenza virus challenge model. While the VRP<sub>3000</sub> vaccine's immune responses in the aged were sufficient to protect against lethal homologous and heterologous challenge, our data suggest that innate defects within the VRP<sub>3014</sub> platform mediate vaccine failure. Exploration into the mechanism(s) of successful vaccination in the immunosenescent should aid in the development of successful vaccine strategies for other viral diseases disproportionately affecting the elderly, like West Nile virus, influenza virus, norovirus, or other emerging viruses of the future.</EA><CC>002A05C10</CC><FD>Souris; Influenzavirus; Coronavirus; Vaccination; Syndrome respiratoire aigu sévère</FD><FG>Rodentia; Mammalia; Vertebrata; Orthomyxoviridae; Virus; Coronaviridae; Nidovirales; Pathologie de l'appareil respiratoire; Virose; Infection; Pathologie des poumons</FG><ED>Mouse; Influenzavirus; Coronavirus; Vaccination; Severe acute respiratory syndrome</ED><EG>Rodentia; Mammalia; Vertebrata; Orthomyxoviridae; Virus; Coronaviridae; Nidovirales; Respiratory disease; Viral disease; Infection; Lung disease</EG><SD>Ratón; Influenzavirus; Coronavirus; Vacunación; Síndrome respiratorio agudo severo</SD><LO>INIST-13592.354000191891830190</LO><ID>11-0091204</ID></server></inist></record>Pour manipuler ce document sous Unix (Dilib)
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