Increasing the Safety Profile of the Master Donor Live Attenuated Influenza Vaccine.
Identifieur interne : 000012 ( Main/Exploration ); précédent : 000011; suivant : 000013Increasing the Safety Profile of the Master Donor Live Attenuated Influenza Vaccine.
Auteurs : Thomas A. Hilimire [États-Unis] ; Aitor Nogales [États-Unis] ; Kevin Chiem [États-Unis] ; Javier Ortego [Espagne] ; Luis Martinez-Sobrido [États-Unis]Source :
- Pathogens (Basel, Switzerland) [ 2076-0817 ] ; 2020.
Abstract
Seasonal influenza epidemics remain one of the largest public health burdens nowadays. The best and most effective strategy to date in preventing influenza infection is a worldwide vaccination campaign. Currently, two vaccines are available to the public for the treatment of influenza infection, the chemically Inactivated Influenza Vaccine (IIV) and the Live Attenuated Influenza Vaccine (LAIV). However, the LAIV is not recommended for parts of the population, such as children under the age of two, immunocompromised individuals, the elderly, and pregnant adults. In order to improve the safety of the LAIV and make it available to more of the population, we sought to further attenuate the LAIV. In this study, we demonstrate that the influenza A virus (IAV) master donor virus (MDV) A/Ann Arbor/6/60 H2N2 LAIV can inhibit host gene expression using both the PA-X and NS1 proteins. Furthermore, we show that by removing PA-X, we can limit the replication of the MDV LAIV in a mouse model, while maintaining full protective efficacy. This work demonstrates a broadly applicable strategy of tuning the amount of host antiviral responses induced by the IAV MDV for the development of newer and safer LAIVs. Moreover, our results also demonstrate, for the first time, the feasibility of genetically manipulating the backbone of the IAV MDV to improve the efficacy of the current IAV LAIV.
DOI: 10.3390/pathogens9020086
PubMed: 32013198
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000001
- to stream PubMed, to step Curation: 000001
- to stream PubMed, to step Checkpoint: 000002
- to stream Ncbi, to step Merge: 001043
- to stream Ncbi, to step Curation: 001043
- to stream Ncbi, to step Checkpoint: 001043
- to stream Main, to step Merge: 000012
- to stream Main, to step Curation: 000012
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Increasing the Safety Profile of the Master Donor Live Attenuated Influenza Vaccine.</title><author><name sortKey="Hilimire, Thomas A" sort="Hilimire, Thomas A" uniqKey="Hilimire T" first="Thomas A" last="Hilimire">Thomas A. Hilimire</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642</wicri:regionArea><wicri:noRegion>NY 14642</wicri:noRegion></affiliation></author><author><name sortKey="Nogales, Aitor" sort="Nogales, Aitor" uniqKey="Nogales A" first="Aitor" last="Nogales">Aitor Nogales</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642</wicri:regionArea><wicri:noRegion>NY 14642</wicri:noRegion></affiliation></author><author><name sortKey="Chiem, Kevin" sort="Chiem, Kevin" uniqKey="Chiem K" first="Kevin" last="Chiem">Kevin Chiem</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642</wicri:regionArea><wicri:noRegion>NY 14642</wicri:noRegion></affiliation></author><author><name sortKey="Ortego, Javier" sort="Ortego, Javier" uniqKey="Ortego J" first="Javier" last="Ortego">Javier Ortego</name><affiliation wicri:level="3"><nlm:affiliation>Center for Animal Health Research, INIA-CISA, 28130 Valdeolmos, Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Center for Animal Health Research, INIA-CISA, 28130 Valdeolmos, Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName></affiliation></author><author><name sortKey="Martinez Sobrido, Luis" sort="Martinez Sobrido, Luis" uniqKey="Martinez Sobrido L" first="Luis" last="Martinez-Sobrido">Luis Martinez-Sobrido</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642</wicri:regionArea><wicri:noRegion>NY 14642</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32013198</idno><idno type="pmid">32013198</idno><idno type="doi">10.3390/pathogens9020086</idno><idno type="wicri:Area/PubMed/Corpus">000001</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000001</idno><idno type="wicri:Area/PubMed/Curation">000001</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000001</idno><idno type="wicri:Area/PubMed/Checkpoint">000002</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000002</idno><idno type="wicri:Area/Ncbi/Merge">001043</idno><idno type="wicri:Area/Ncbi/Curation">001043</idno><idno type="wicri:Area/Ncbi/Checkpoint">001043</idno><idno type="wicri:doubleKey">2076-0817:2020:Hilimire T:increasing:the:safety</idno><idno type="wicri:Area/Main/Merge">000012</idno><idno type="wicri:Area/Main/Curation">000012</idno><idno type="wicri:Area/Main/Exploration">000012</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Increasing the Safety Profile of the Master Donor Live Attenuated Influenza Vaccine.</title><author><name sortKey="Hilimire, Thomas A" sort="Hilimire, Thomas A" uniqKey="Hilimire T" first="Thomas A" last="Hilimire">Thomas A. Hilimire</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642</wicri:regionArea><wicri:noRegion>NY 14642</wicri:noRegion></affiliation></author><author><name sortKey="Nogales, Aitor" sort="Nogales, Aitor" uniqKey="Nogales A" first="Aitor" last="Nogales">Aitor Nogales</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642</wicri:regionArea><wicri:noRegion>NY 14642</wicri:noRegion></affiliation></author><author><name sortKey="Chiem, Kevin" sort="Chiem, Kevin" uniqKey="Chiem K" first="Kevin" last="Chiem">Kevin Chiem</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642</wicri:regionArea><wicri:noRegion>NY 14642</wicri:noRegion></affiliation></author><author><name sortKey="Ortego, Javier" sort="Ortego, Javier" uniqKey="Ortego J" first="Javier" last="Ortego">Javier Ortego</name><affiliation wicri:level="3"><nlm:affiliation>Center for Animal Health Research, INIA-CISA, 28130 Valdeolmos, Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Center for Animal Health Research, INIA-CISA, 28130 Valdeolmos, Madrid</wicri:regionArea><placeName><settlement type="city">Madrid</settlement><region nuts="2" type="region">Communauté de Madrid</region></placeName></affiliation></author><author><name sortKey="Martinez Sobrido, Luis" sort="Martinez Sobrido, Luis" uniqKey="Martinez Sobrido L" first="Luis" last="Martinez-Sobrido">Luis Martinez-Sobrido</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642</wicri:regionArea><wicri:noRegion>NY 14642</wicri:noRegion></affiliation></author></analytic><series><title level="j">Pathogens (Basel, Switzerland)</title><idno type="ISSN">2076-0817</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Seasonal influenza epidemics remain one of the largest public health burdens nowadays. The best and most effective strategy to date in preventing influenza infection is a worldwide vaccination campaign. Currently, two vaccines are available to the public for the treatment of influenza infection, the chemically Inactivated Influenza Vaccine (IIV) and the Live Attenuated Influenza Vaccine (LAIV). However, the LAIV is not recommended for parts of the population, such as children under the age of two, immunocompromised individuals, the elderly, and pregnant adults. In order to improve the safety of the LAIV and make it available to more of the population, we sought to further attenuate the LAIV. In this study, we demonstrate that the influenza A virus (IAV) master donor virus (MDV) A/Ann Arbor/6/60 H2N2 LAIV can inhibit host gene expression using both the PA-X and NS1 proteins. Furthermore, we show that by removing PA-X, we can limit the replication of the MDV LAIV in a mouse model, while maintaining full protective efficacy. This work demonstrates a broadly applicable strategy of tuning the amount of host antiviral responses induced by the IAV MDV for the development of newer and safer LAIVs. Moreover, our results also demonstrate, for the first time, the feasibility of genetically manipulating the backbone of the IAV MDV to improve the efficacy of the current IAV LAIV.</div></front></TEI><affiliations><list><country><li>Espagne</li><li>États-Unis</li></country><region><li>Communauté de Madrid</li></region><settlement><li>Madrid</li></settlement></list><tree><country name="États-Unis"><noRegion><name sortKey="Hilimire, Thomas A" sort="Hilimire, Thomas A" uniqKey="Hilimire T" first="Thomas A" last="Hilimire">Thomas A. Hilimire</name></noRegion><name sortKey="Chiem, Kevin" sort="Chiem, Kevin" uniqKey="Chiem K" first="Kevin" last="Chiem">Kevin Chiem</name><name sortKey="Martinez Sobrido, Luis" sort="Martinez Sobrido, Luis" uniqKey="Martinez Sobrido L" first="Luis" last="Martinez-Sobrido">Luis Martinez-Sobrido</name><name sortKey="Nogales, Aitor" sort="Nogales, Aitor" uniqKey="Nogales A" first="Aitor" last="Nogales">Aitor Nogales</name></country><country name="Espagne"><region name="Communauté de Madrid"><name sortKey="Ortego, Javier" sort="Ortego, Javier" uniqKey="Ortego J" first="Javier" last="Ortego">Javier Ortego</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/H2N2V1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000012 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000012 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= H2N2V1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:32013198
|texte= Increasing the Safety Profile of the Master Donor Live Attenuated Influenza Vaccine.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:32013198" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a H2N2V1
| This area was generated with Dilib version V0.6.33. |  |