ChloroquineV1, Main, Exploration, bibRecord, 000A78

Antibody-dependent enhancement of influenza disease promoted by increase in hemagglutinin stem flexibility and virus fusion kinetics

Identifieur interne : 000A78 ( Main/Exploration ); précédent : 000A77; suivant : 000A79

Antibody-dependent enhancement of influenza disease promoted by increase in hemagglutinin stem flexibility and virus fusion kinetics

Auteurs : Katie L. Winarski ; Juanjie Tang ; Laura Klenow ; Jeehyun Lee ; Elizabeth M. Coyle ; Jody Manischewitz ; Hannah L. Turner ; Kazuyo Takeda ; Andrew B. Ward ; Hana Golding ; Surender Khurana

Source :

Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2019.

RBID : PMC:6660725

Abstract

Significance

Next-generation influenza vaccines and broadly neutralizing antibodies (bNAbs) are in clinical development. Some of these do not block virus–receptor interactions and thus are predicted to provide protection via alternative mechanisms at the postentry stage or use Fc-dependent mechanisms. Nonneutralizing antibodies have the potential to mediate enhancement of respiratory disease (ERD). Our study describes ADE with two different functional MAbs that destabilized HA stem domain, increased influenza virus fusion kinetics, and led to enhanced lung pathology and ERD in a dose-dependent manner in a mice model. This study underlines careful preclinical evaluation of next-generation influenza vaccines or antibody-based therapeutics that do not block influenza virus receptor binding.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660725

DOI: 10.1073/pnas.1821317116
PubMed: 31296560
PubMed Central: 6660725

Affiliations:

Le document en format XML

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<author><name sortKey="Winarski, Katie L" sort="Winarski, Katie L" uniqKey="Winarski K" first="Katie L." last="Winarski">Katie L. Winarski</name>
<affiliation><nlm:aff id="aff1">Division of Viral Products, Center for Biologics Evaluation and Research,<institution>Food and Drug Administration</institution>
, Silver Spring,<addr-line>MD</addr-line>
 20993;</nlm:aff>
</affiliation>
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<author><name sortKey="Tang, Juanjie" sort="Tang, Juanjie" uniqKey="Tang J" first="Juanjie" last="Tang">Juanjie Tang</name>
<affiliation><nlm:aff id="aff1">Division of Viral Products, Center for Biologics Evaluation and Research,<institution>Food and Drug Administration</institution>
, Silver Spring,<addr-line>MD</addr-line>
 20993;</nlm:aff>
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<author><name sortKey="Klenow, Laura" sort="Klenow, Laura" uniqKey="Klenow L" first="Laura" last="Klenow">Laura Klenow</name>
<affiliation><nlm:aff id="aff1">Division of Viral Products, Center for Biologics Evaluation and Research,<institution>Food and Drug Administration</institution>
, Silver Spring,<addr-line>MD</addr-line>
 20993;</nlm:aff>
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, Silver Spring,<addr-line>MD</addr-line>
 20993;</nlm:aff>
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 20993;</nlm:aff>
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 20993;</nlm:aff>
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 92037</nlm:aff>
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 20993;</nlm:aff>
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 92037</nlm:aff>
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, Silver Spring,<addr-line>MD</addr-line>
 20993;</nlm:aff>
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 20993;</nlm:aff>
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 20993;</nlm:aff>
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 20993;</nlm:aff>
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 20993;</nlm:aff>
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 20993;</nlm:aff>
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, Silver Spring,<addr-line>MD</addr-line>
 20993;</nlm:aff>
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, La Jolla,<addr-line>CA</addr-line>
 92037</nlm:aff>
</affiliation>
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, Silver Spring,<addr-line>MD</addr-line>
 20993;</nlm:aff>
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, La Jolla,<addr-line>CA</addr-line>
 92037</nlm:aff>
</affiliation>
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, Silver Spring,<addr-line>MD</addr-line>
 20993;</nlm:aff>
</affiliation>
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, Silver Spring,<addr-line>MD</addr-line>
 20993;</nlm:aff>
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<front><div type="abstract" xml:lang="en"><title>Significance</title>
<p>Next-generation influenza vaccines and broadly neutralizing antibodies (bNAbs) are in clinical development. Some of these do not block virus–receptor interactions and thus are predicted to provide protection via alternative mechanisms at the postentry stage or use Fc-dependent mechanisms. Nonneutralizing antibodies have the potential to mediate enhancement of respiratory disease (ERD). Our study describes ADE with two different functional MAbs that destabilized HA stem domain, increased influenza virus fusion kinetics, and led to enhanced lung pathology and ERD in a dose-dependent manner in a mice model. This study underlines careful preclinical evaluation of next-generation influenza vaccines or antibody-based therapeutics that do not block influenza virus receptor binding.</p>
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<tree><noCountry><name sortKey="Coyle, Elizabeth M" sort="Coyle, Elizabeth M" uniqKey="Coyle E" first="Elizabeth M." last="Coyle">Elizabeth M. Coyle</name>
<name sortKey="Golding, Hana" sort="Golding, Hana" uniqKey="Golding H" first="Hana" last="Golding">Hana Golding</name>
<name sortKey="Khurana, Surender" sort="Khurana, Surender" uniqKey="Khurana S" first="Surender" last="Khurana">Surender Khurana</name>
<name sortKey="Klenow, Laura" sort="Klenow, Laura" uniqKey="Klenow L" first="Laura" last="Klenow">Laura Klenow</name>
<name sortKey="Lee, Jeehyun" sort="Lee, Jeehyun" uniqKey="Lee J" first="Jeehyun" last="Lee">Jeehyun Lee</name>
<name sortKey="Manischewitz, Jody" sort="Manischewitz, Jody" uniqKey="Manischewitz J" first="Jody" last="Manischewitz">Jody Manischewitz</name>
<name sortKey="Takeda, Kazuyo" sort="Takeda, Kazuyo" uniqKey="Takeda K" first="Kazuyo" last="Takeda">Kazuyo Takeda</name>
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Antibody-dependent enhancement of influenza disease promoted by increase in hemagglutinin stem flexibility and virus fusion kinetics

Antibody-dependent enhancement of influenza disease promoted by increase in hemagglutinin stem flexibility and virus fusion kinetics

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Abstract

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