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Article: Generation of DelNS1 Influenza Viruses: a Strategy for Optimizing Live Attenuated Influenza Vaccines

TitleGeneration of DelNS1 Influenza Viruses: a Strategy for Optimizing Live Attenuated Influenza Vaccines
Authors
Keywordslive attenuated vaccine
NS1
influenza vaccines
Issue Date2019
PublisherAmerican Society for Microbiology: Open Access Journals. The Journal's web site is located at http://mbio.asm.org
Citation
mBio, 2019, v. 10 n. 5, p. article no. e02180-19 How to Cite?
AbstractNonstructural protein 1 (NS1) of influenza virus is a key virulence element with multifunctional roles in virus replication and a potent antagonist of host immune response. Deletion of NS1 (DelNS1) would create a safer and more extensively immunogenic live attenuated influenza virus (LAIV) vaccine. However, DelNS1 viruses are very difficult to grow in regular vaccine-producing systems, which has hampered the application of DelNS1 LAIV vaccines in humans. We have developed two master backbones of deleted-NS1 (DelNS1) viral genomes from influenza A or B viruses which contain novel adaptive mutations to support DelNS1-LAIV replication. These DelNS1-LAIVs are highly attenuated in human cells in vitro and nonpathogenic in mice but replicate well in vaccine-producing cells. Both influenza A and influenza B DelNS1 LAIVs grow better at 33°C than at 37 to 39°C. Vaccination with DelNS1 LAIV performed once is enough to provide potent protection against lethal challenge with homologous virus and strong long-lasting cross protection against heterosubtypic or antigenically distantly related influenza viruses in mice. Mechanistic investigations revealed that DelNS1-LAIVs induce cross protective neutralizing antibody and CD8 and CD4 T cell immunities. Importantly, it has been shown that DelNS1-LAIV can be used to enhance specific anti-influenza immunity through expression of additional antigens from the deleted-NS1 site. Generation of DelNS1 viruses which are nonpathogenic and able to grow in vaccine-producing systems is an important strategy for making highly immunogenic LAIV vaccines that induce broad cross protective immunity against seasonal and emerging influenza.
Persistent Identifierhttp://hdl.handle.net/10722/277361
ISSN
2017 Impact Factor: 6.689
2015 SCImago Journal Rankings: 3.543
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorWang, P-
dc.contributor.authorZheng, M-
dc.contributor.authorLau, SY-
dc.contributor.authorCHEN, P-
dc.contributor.authorMok, BWY-
dc.contributor.authorLiu, S-
dc.contributor.authorLIU, H-
dc.contributor.authorHuang, X-
dc.contributor.authorCREMIN, CJ-
dc.contributor.authorSong, W-
dc.contributor.authorChen, Y-
dc.contributor.authorWong, YC-
dc.contributor.authorHUANG, H-
dc.contributor.authorTo, KKW-
dc.contributor.authorChen, Z-
dc.contributor.authorXia, N-
dc.contributor.authorYuen, KY-
dc.contributor.authorChen, H-
dc.date.accessioned2019-09-20T08:49:36Z-
dc.date.available2019-09-20T08:49:36Z-
dc.date.issued2019-
dc.identifier.citationmBio, 2019, v. 10 n. 5, p. article no. e02180-19-
dc.identifier.issn2150-7511-
dc.identifier.urihttp://hdl.handle.net/10722/277361-
dc.description.abstractNonstructural protein 1 (NS1) of influenza virus is a key virulence element with multifunctional roles in virus replication and a potent antagonist of host immune response. Deletion of NS1 (DelNS1) would create a safer and more extensively immunogenic live attenuated influenza virus (LAIV) vaccine. However, DelNS1 viruses are very difficult to grow in regular vaccine-producing systems, which has hampered the application of DelNS1 LAIV vaccines in humans. We have developed two master backbones of deleted-NS1 (DelNS1) viral genomes from influenza A or B viruses which contain novel adaptive mutations to support DelNS1-LAIV replication. These DelNS1-LAIVs are highly attenuated in human cells in vitro and nonpathogenic in mice but replicate well in vaccine-producing cells. Both influenza A and influenza B DelNS1 LAIVs grow better at 33°C than at 37 to 39°C. Vaccination with DelNS1 LAIV performed once is enough to provide potent protection against lethal challenge with homologous virus and strong long-lasting cross protection against heterosubtypic or antigenically distantly related influenza viruses in mice. Mechanistic investigations revealed that DelNS1-LAIVs induce cross protective neutralizing antibody and CD8 and CD4 T cell immunities. Importantly, it has been shown that DelNS1-LAIV can be used to enhance specific anti-influenza immunity through expression of additional antigens from the deleted-NS1 site. Generation of DelNS1 viruses which are nonpathogenic and able to grow in vaccine-producing systems is an important strategy for making highly immunogenic LAIV vaccines that induce broad cross protective immunity against seasonal and emerging influenza.-
dc.languageeng-
dc.publisherAmerican Society for Microbiology: Open Access Journals. The Journal's web site is located at http://mbio.asm.org-
dc.relation.ispartofmBio-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectlive attenuated vaccine-
dc.subjectNS1-
dc.subjectinfluenza vaccines-
dc.titleGeneration of DelNS1 Influenza Viruses: a Strategy for Optimizing Live Attenuated Influenza Vaccines-
dc.typeArticle-
dc.identifier.emailWang, P: puiwang@hkucc.hku.hk-
dc.identifier.emailLau, SY: sylau926@hkucc.hku.hk-
dc.identifier.emailMok, BWY: bobomok@hku.hk-
dc.identifier.emailTo, KKW: kelvinto@hku.hk-
dc.identifier.emailChen, Z: zchenai@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.emailChen, H: hlchen@hku.hk-
dc.identifier.authorityTo, KKW=rp01384-
dc.identifier.authorityChen, Z=rp00243-
dc.identifier.authorityYuen, KY=rp00366-
dc.identifier.authorityChen, H=rp00383-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1128/mBio.02180-19-
dc.identifier.pmid31530680-
dc.identifier.pmcidPMC6751066-
dc.identifier.scopuseid_2-s2.0-85072283310-
dc.identifier.hkuros305886-
dc.identifier.volume10-
dc.identifier.issue5-
dc.identifier.spagearticle no. e02180-
dc.identifier.epage19-
dc.publisher.placeUnited States-

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