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Conference Paper: Characterization of mutations associated with cold adapted properties in DelNS1 influenza viruses; potential for new live attenuated influenza vaccine development
Title | Characterization of mutations associated with cold adapted properties in DelNS1 influenza viruses; potential for new live attenuated influenza vaccine development |
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Authors | |
Issue Date | 2016 |
Publisher | International Society for Influenza and Other Respiratory Virus Diseases. |
Citation | The 9th International Scientific Conference of Options for the Control of Influenza (Options-9), Chicago, IL., 24-28 August 2016. In Conference Program, 2016, p. 297, abstract no. P-619 How to Cite? |
Abstract | BACKGROUND: Our previous study identified an A14U substitution in the M
segment non-coding region that supports replication of NS1-deleted (DelNS1)
virus derived from the A/WSN/33 strain. Construction of DelNS1 versions of
other influenza strains revealed that different strains require different adaptive
mutations to restore virus replication when NS1 is deleted.
METHOD: Using a similar strategy, a panel of DelNS1 viruses derived from WSN
H1N1, 2009 H1N1, H5N1 and H7N9 were constructed and characterized. These
DelNS1 viruses are able to replicate in both MDCK cells and eggs, are avirulent
in mice, and can provide cross protection against lethal challenge with
heterosubtypic viruses in animals. In the DelNS1 virus derived from 2009 H1N1
virus, we also identified substitutions which facilitate virus replication at lower
temperatures (30-33oC) but limit virus replication at higher temperatures
(37-39oC). We found this cold adapted DelNS1 2009 H1N1 virus to be able
to replicate to comparable titers to the wild type virus in MDCK cells and
embryonated chicken eggs, but to cause no disease symptoms in mice, even at
the highest dose tested. Furthermore, mice receiving nasal immunization with
cold adapted DelNS1 2009 H1N1 virus are protected from lethal challenges
with H1N1, H5N1 and H7N9 viruses. The DelNS1 2009 H1N1 virus appears
to provide better protection than the currently available cold adapted live
attenuated H1N1 virus vaccine strain in animal experiments, suggesting DelNS1
may confer an advantage augment the effectiveness of live attenuated flu
vaccines , promoting the induction of stronger and broader immunity to
influenza virus infection. Finally, we extended the scope of our DelNS1 system
to construct a recombinant virus containing the RBD domain of MERS-CoV
in the place of NS1, and found that it is able to protect against infection with
MERS-CoV in the DPP4-transgenic mouse model.
CONCLUSION: This study characterizes the substitutions required to support
virus replication at lower temperature in the absence of NS1 protein in various
influenza virus strains, and demonstrates that the combination of DelNS1 and
cold adapted properties may have potential as a strategy to develop better and
safer live attenuated influenza vaccines. |
Description | Poster Sessions: no. P-619 |
Persistent Identifier | http://hdl.handle.net/10722/232505 |
DC Field | Value | Language |
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dc.contributor.author | Zheng, M | - |
dc.contributor.author | Wang, P | - |
dc.contributor.author | Lau, SY | - |
dc.contributor.author | Huang, X | - |
dc.contributor.author | Mok, BWY | - |
dc.contributor.author | Liu, S | - |
dc.contributor.author | Liu, H | - |
dc.contributor.author | Liu, Y | - |
dc.contributor.author | Chen, H | - |
dc.date.accessioned | 2016-09-20T05:30:29Z | - |
dc.date.available | 2016-09-20T05:30:29Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | The 9th International Scientific Conference of Options for the Control of Influenza (Options-9), Chicago, IL., 24-28 August 2016. In Conference Program, 2016, p. 297, abstract no. P-619 | - |
dc.identifier.uri | http://hdl.handle.net/10722/232505 | - |
dc.description | Poster Sessions: no. P-619 | - |
dc.description.abstract | BACKGROUND: Our previous study identified an A14U substitution in the M segment non-coding region that supports replication of NS1-deleted (DelNS1) virus derived from the A/WSN/33 strain. Construction of DelNS1 versions of other influenza strains revealed that different strains require different adaptive mutations to restore virus replication when NS1 is deleted. METHOD: Using a similar strategy, a panel of DelNS1 viruses derived from WSN H1N1, 2009 H1N1, H5N1 and H7N9 were constructed and characterized. These DelNS1 viruses are able to replicate in both MDCK cells and eggs, are avirulent in mice, and can provide cross protection against lethal challenge with heterosubtypic viruses in animals. In the DelNS1 virus derived from 2009 H1N1 virus, we also identified substitutions which facilitate virus replication at lower temperatures (30-33oC) but limit virus replication at higher temperatures (37-39oC). We found this cold adapted DelNS1 2009 H1N1 virus to be able to replicate to comparable titers to the wild type virus in MDCK cells and embryonated chicken eggs, but to cause no disease symptoms in mice, even at the highest dose tested. Furthermore, mice receiving nasal immunization with cold adapted DelNS1 2009 H1N1 virus are protected from lethal challenges with H1N1, H5N1 and H7N9 viruses. The DelNS1 2009 H1N1 virus appears to provide better protection than the currently available cold adapted live attenuated H1N1 virus vaccine strain in animal experiments, suggesting DelNS1 may confer an advantage augment the effectiveness of live attenuated flu vaccines , promoting the induction of stronger and broader immunity to influenza virus infection. Finally, we extended the scope of our DelNS1 system to construct a recombinant virus containing the RBD domain of MERS-CoV in the place of NS1, and found that it is able to protect against infection with MERS-CoV in the DPP4-transgenic mouse model. CONCLUSION: This study characterizes the substitutions required to support virus replication at lower temperature in the absence of NS1 protein in various influenza virus strains, and demonstrates that the combination of DelNS1 and cold adapted properties may have potential as a strategy to develop better and safer live attenuated influenza vaccines. | - |
dc.language | eng | - |
dc.publisher | International Society for Influenza and Other Respiratory Virus Diseases. | - |
dc.relation.ispartof | International Scientific Conference of Options for the Control of Influenza, Options-9 | - |
dc.title | Characterization of mutations associated with cold adapted properties in DelNS1 influenza viruses; potential for new live attenuated influenza vaccine development | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Zheng, M: zhengmin@hku.hk | - |
dc.identifier.email | Wang, P: puiwang@hkucc.hku.hk | - |
dc.identifier.email | Lau, SY: sylau926@hkucc.hku.hk | - |
dc.identifier.email | Mok, BWY: bobomok@hku.hk | - |
dc.identifier.email | Liu, Y: yenchin@hku.hk | - |
dc.identifier.email | Chen, H: hlchen@hku.hk | - |
dc.identifier.authority | Chen, H=rp00383 | - |
dc.identifier.hkuros | 267050 | - |
dc.identifier.spage | 297, abstract no. P-619 | - |
dc.identifier.epage | 297, abstract no. P-619 | - |
dc.publisher.place | United States | - |