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Monoclonal antibody against N2 neuraminidase of cold adapted A/Leningrad/134/17/57 (H2N2) enables efficient generation of live attenuated influenza vaccines

Identifieur interne : 000792 ( Pmc/Curation ); précédent : 000791; suivant : 000793

Monoclonal antibody against N2 neuraminidase of cold adapted A/Leningrad/134/17/57 (H2N2) enables efficient generation of live attenuated influenza vaccines

Auteurs : Svetlana Shcherbik [États-Unis] ; Paul Carney [États-Unis] ; Nicholas Pearce [États-Unis] ; James Stevens [États-Unis] ; Vivien G. Dugan [États-Unis] ; David E. Wentworth [États-Unis] ; Tatiana Bousse [États-Unis]

Source :

RBID : PMC:6498426

Abstract

Cold adapted influenza virus A/Leningrad/134/17/57 (H2N2) is a reliable master donor virus (Len/17-MDV) for preparing live attenuated influenza vaccines (LAIV). LAIVs are 6:2 reasortants that contain 6 segments of Len/17-MDV and the hemagglutinin (HA) and neuraminidase (NA) of contemporary circulating influenza A viruses. The problem with the classical reassortment procedure used to generate LAIVs is that there is limited selection pressure against NA of the Len/17-MDV resulting in 7:1 reassortants with desired HA only, which are not suitable LAIVs. The monoclonal antibodies (mAb) directed against the N2 of Len/17-MDV were generated. 10C4–8E7 mAb inhibits cell-to-cell spread of viruses containing the Len/17-MDV N2, but not viruses with the related N2 from contemporary H3N2 viruses. 10C4–8E7 antibody specifically inhibited the Len/17-MDV replication in vitro and in ovo but didn’t inhibit replication of H3N2 or H1N1pdm09 reassortants. Our data demonstrate that addition of 10C4–8E7 in the classical reassortment improves efficiency of LAIV production.


Url:
DOI: 10.1016/j.virol.2018.07.005
PubMed: 30014859
PubMed Central: 6498426

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PMC:6498426

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<div type="abstract" xml:lang="en">
<p id="P1">Cold adapted influenza virus A/Leningrad/134/17/57 (H2N2) is a reliable master donor virus (Len/17-MDV) for preparing live attenuated influenza vaccines (LAIV). LAIVs are 6:2 reasortants that contain 6 segments of Len/17-MDV and the hemagglutinin (HA) and neuraminidase (NA) of contemporary circulating influenza A viruses. The problem with the classical reassortment procedure used to generate LAIVs is that there is limited selection pressure against NA of the Len/17-MDV resulting in 7:1 reassortants with desired HA only, which are not suitable LAIVs. The monoclonal antibodies (mAb) directed against the N2 of Len/17-MDV were generated. 10C4–8E7 mAb inhibits cell-to-cell spread of viruses containing the Len/17-MDV N2, but not viruses with the related N2 from contemporary H3N2 viruses. 10C4–8E7 antibody specifically inhibited the Len/17-MDV replication
<italic>in vitro</italic>
and
<italic>in ovo</italic>
but didn’t inhibit replication of H3N2 or H1N1pdm09 reassortants. Our data demonstrate that addition of 10C4–8E7 in the classical reassortment improves efficiency of LAIV production.</p>
</div>
</front>
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<name>
<surname>Shcherbik</surname>
<given-names>Svetlana</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
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<name>
<surname>Carney</surname>
<given-names>Paul</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
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<xref ref-type="aff" rid="A2">b</xref>
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<name>
<surname>Stevens</surname>
<given-names>James</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
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<name>
<surname>Dugan</surname>
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<name>
<surname>Bousse</surname>
<given-names>Tatiana</given-names>
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Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, United States</aff>
<aff id="A2">
<label>b</label>
Battelle, Atlanta, GA 30329, United States</aff>
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Corresponding author.
<email>gsx8@cdc.gov</email>
(T. Bousse).</corresp>
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<pub-date pub-type="nihms-submitted">
<day>23</day>
<month>4</month>
<year>2019</year>
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<month>7</month>
<year>2018</year>
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<pub-date pub-type="ppub">
<month>9</month>
<year>2018</year>
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<pub-date pub-type="pmc-release">
<day>03</day>
<month>5</month>
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<fpage>65</fpage>
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<pmc-comment>elocation-id from pubmed: 10.1016/j.virol.2018.07.005</pmc-comment>
<abstract id="ABS1">
<p id="P1">Cold adapted influenza virus A/Leningrad/134/17/57 (H2N2) is a reliable master donor virus (Len/17-MDV) for preparing live attenuated influenza vaccines (LAIV). LAIVs are 6:2 reasortants that contain 6 segments of Len/17-MDV and the hemagglutinin (HA) and neuraminidase (NA) of contemporary circulating influenza A viruses. The problem with the classical reassortment procedure used to generate LAIVs is that there is limited selection pressure against NA of the Len/17-MDV resulting in 7:1 reassortants with desired HA only, which are not suitable LAIVs. The monoclonal antibodies (mAb) directed against the N2 of Len/17-MDV were generated. 10C4–8E7 mAb inhibits cell-to-cell spread of viruses containing the Len/17-MDV N2, but not viruses with the related N2 from contemporary H3N2 viruses. 10C4–8E7 antibody specifically inhibited the Len/17-MDV replication
<italic>in vitro</italic>
and
<italic>in ovo</italic>
but didn’t inhibit replication of H3N2 or H1N1pdm09 reassortants. Our data demonstrate that addition of 10C4–8E7 in the classical reassortment improves efficiency of LAIV production.</p>
</abstract>
<kwd-group>
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