Successful Vaccination Strategies That Protect Aged Mice from Lethal Challenge from Influenza Virus and Heterologous Severe Acute Respiratory Syndrome Coronavirus ▿
Identifieur interne : 002439 ( Main/Exploration ); précédent : 002438; suivant : 002440Successful 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 ] ; 2010.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (sang), Anticorps neutralisants (sang), Femelle, Humains, Infections à Orthomyxoviridae (), Infections à Orthomyxoviridae (immunologie), Infections à Orthomyxoviridae (mortalité), Modèles animaux de maladie humaine, Orthomyxoviridae (pathogénicité), Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (immunologie), Réplicon, Souris, Souris de lignée BALB C, Syndrome respiratoire aigu sévère (), Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (mortalité), Syndrome respiratoire aigu sévère (virologie), Tests de neutralisation, Vaccination, Vaccins antiviraux (administration et posologie), Vaccins antiviraux (génétique), Vaccins antiviraux (immunologie), Vaccins atténués (administration et posologie), Vaccins atténués (génétique), Vaccins atténués (immunologie), Vecteurs génétiques, Vieillissement (immunologie), Virion (génétique), Virion (immunologie), Virion (métabolisme), Virus de l'encéphalite équine du Venezuela (génétique), Virus de l'encéphalite équine du Venezuela (immunologie), Virus de l'encéphalite équine du Venezuela (physiologie), Virus du SRAS (pathogénicité).
- MESH :
- administration et posologie : Vaccins antiviraux, Vaccins atténués.
- génétique : Protéines de l'enveloppe virale, Vaccins antiviraux, Vaccins atténués, Virion, Virus de l'encéphalite équine du Venezuela.
- immunologie : Infections à Orthomyxoviridae, Protéines de l'enveloppe virale, Syndrome respiratoire aigu sévère, Vaccins antiviraux, Vaccins atténués, Vieillissement, Virion, Virus de l'encéphalite équine du Venezuela.
- mortalité : Infections à Orthomyxoviridae, Syndrome respiratoire aigu sévère.
- métabolisme : Virion.
- pathogénicité : Orthomyxoviridae, Virus du SRAS.
- physiologie : Virus de l'encéphalite équine du Venezuela.
- sang : Anticorps antiviraux, Anticorps neutralisants.
- virologie : Syndrome respiratoire aigu sévère.
- Animaux, Femelle, Humains, Infections à Orthomyxoviridae, Modèles animaux de maladie humaine, Réplicon, Souris, Souris de lignée BALB C, Syndrome respiratoire aigu sévère, Tests de neutralisation, Vaccination, Vecteurs génétiques.
English descriptors
- KwdEn :
- Aging (immunology), Animals, Antibodies, Neutralizing (blood), Antibodies, Viral (blood), Disease Models, Animal, Encephalitis Virus, Venezuelan Equine (genetics), Encephalitis Virus, Venezuelan Equine (immunology), Encephalitis Virus, Venezuelan Equine (physiology), Female, Genetic Vectors, Humans, Mice, Mice, Inbred BALB C, Neutralization Tests, Orthomyxoviridae (pathogenicity), Orthomyxoviridae Infections (immunology), Orthomyxoviridae Infections (mortality), Orthomyxoviridae Infections (prevention & control), Replicon, SARS Virus (pathogenicity), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (mortality), Severe Acute Respiratory Syndrome (prevention & control), Severe Acute Respiratory Syndrome (virology), Vaccination, Vaccines, Attenuated (administration & dosage), Vaccines, Attenuated (genetics), Vaccines, Attenuated (immunology), Viral Envelope Proteins (genetics), Viral Envelope Proteins (immunology), Viral Vaccines (administration & dosage), Viral Vaccines (genetics), Viral Vaccines (immunology), Virion (genetics), Virion (immunology), Virion (metabolism).
- MESH :
- chemical , administration & dosage : Vaccines, Attenuated, Viral Vaccines.
- chemical , blood : Antibodies, Neutralizing, Antibodies, Viral.
- genetics : Encephalitis Virus, Venezuelan Equine, Vaccines, Attenuated, Viral Envelope Proteins, Viral Vaccines, Virion.
- immunology : Aging, Encephalitis Virus, Venezuelan Equine, Orthomyxoviridae Infections, Severe Acute Respiratory Syndrome, Vaccines, Attenuated, Viral Envelope Proteins, Viral Vaccines, Virion.
- metabolism : Virion.
- mortality : Orthomyxoviridae Infections, Severe Acute Respiratory Syndrome.
- pathogenicity : Orthomyxoviridae, SARS Virus.
- physiology : Encephalitis Virus, Venezuelan Equine.
- prevention & control : Orthomyxoviridae Infections, Severe Acute Respiratory Syndrome.
- virology : Severe Acute Respiratory Syndrome.
- Animals, Disease Models, Animal, Female, Genetic Vectors, Humans, Mice, Mice, Inbred BALB C, Neutralization Tests, Replicon, Vaccination.
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.
Url:
DOI: 10.1128/JVI.01805-10
PubMed: 20980507
PubMed Central: 3014161
Affiliations:
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Le document en format XML
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Infections (immunology)</term><term>Orthomyxoviridae Infections (mortality)</term><term>Orthomyxoviridae Infections (prevention & control)</term><term>Replicon</term><term>SARS Virus (pathogenicity)</term><term>Severe Acute Respiratory Syndrome (immunology)</term><term>Severe Acute Respiratory Syndrome (mortality)</term><term>Severe Acute Respiratory Syndrome (prevention & control)</term><term>Severe Acute Respiratory Syndrome (virology)</term><term>Vaccination</term><term>Vaccines, Attenuated (administration & dosage)</term><term>Vaccines, Attenuated (genetics)</term><term>Vaccines, Attenuated (immunology)</term><term>Viral Envelope Proteins (genetics)</term><term>Viral Envelope Proteins (immunology)</term><term>Viral Vaccines (administration & dosage)</term><term>Viral Vaccines (genetics)</term><term>Viral Vaccines (immunology)</term><term>Virion (genetics)</term><term>Virion (immunology)</term><term>Virion (metabolism)</term></keywords><keywords scheme="KwdFr" 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Vectors</term><term>Humans</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Neutralization Tests</term><term>Replicon</term><term>Vaccination</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Femelle</term><term>Humains</term><term>Infections à Orthomyxoviridae</term><term>Modèles animaux de maladie humaine</term><term>Réplicon</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Syndrome respiratoire aigu sévère</term><term>Tests de neutralisation</term><term>Vaccination</term><term>Vecteurs génétiques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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.</p></div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><name sortKey="Collier, Martha" sort="Collier, Martha" uniqKey="Collier M" first="Martha" last="Collier">Martha Collier</name><name sortKey="Davis, Nancy" sort="Davis, Nancy" uniqKey="Davis N" first="Nancy" last="Davis">Nancy Davis</name><name sortKey="Donaldson, Eric" sort="Donaldson, Eric" uniqKey="Donaldson E" first="Eric" last="Donaldson">Eric Donaldson</name><name sortKey="Ferris, Martin" sort="Ferris, Martin" uniqKey="Ferris M" first="Martin" last="Ferris">Martin Ferris</name><name sortKey="Funkhouser, William" sort="Funkhouser, William" uniqKey="Funkhouser W" first="William" last="Funkhouser">William Funkhouser</name><name sortKey="Gralinski, Lisa" sort="Gralinski, Lisa" uniqKey="Gralinski L" first="Lisa" last="Gralinski">Lisa Gralinski</name><name sortKey="Heise, Mark" sort="Heise, Mark" uniqKey="Heise M" first="Mark" last="Heise">Mark Heise</name><name sortKey="Johnston, Robert" sort="Johnston, Robert" uniqKey="Johnston R" first="Robert" last="Johnston">Robert Johnston</name><name sortKey="Long, Kristin" sort="Long, Kristin" uniqKey="Long K" first="Kristin" last="Long">Kristin Long</name><name sortKey="Rockx, Barry" sort="Rockx, Barry" uniqKey="Rockx B" first="Barry" last="Rockx">Barry Rockx</name><name sortKey="Sheahan, Timothy" sort="Sheahan, Timothy" uniqKey="Sheahan T" first="Timothy" last="Sheahan">Timothy Sheahan</name><name sortKey="Whitmore, Alan" sort="Whitmore, Alan" uniqKey="Whitmore A" first="Alan" last="Whitmore">Alan Whitmore</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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