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Article: Stalking influenza by vaccination with pre-fusion headless HA mini-stem

TitleStalking influenza by vaccination with pre-fusion headless HA mini-stem
Authors
Issue Date2016
PublisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/srep/index.html
Citation
Scientific Reports, 2016, v. 6, p. article no. 22666 How to Cite?
AbstractInaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies induced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity.
Persistent Identifierhttp://hdl.handle.net/10722/230500
ISSN
2015 Impact Factor: 5.228
2015 SCImago Journal Rankings: 2.073

 

DC FieldValueLanguage
dc.contributor.authorDoak, SA-
dc.contributor.authorMallajosyula, VV-
dc.contributor.authorLi, OTW-
dc.contributor.authorChin, WH-
dc.contributor.authorCarnell, G-
dc.contributor.authorTemperton, N-
dc.contributor.authorVaradarajan, R-
dc.contributor.authorPoon, LML-
dc.date.accessioned2016-08-23T14:17:24Z-
dc.date.available2016-08-23T14:17:24Z-
dc.date.issued2016-
dc.identifier.citationScientific Reports, 2016, v. 6, p. article no. 22666-
dc.identifier.issn2045-2322-
dc.identifier.urihttp://hdl.handle.net/10722/230500-
dc.description.abstractInaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies induced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity.-
dc.languageeng-
dc.publisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/srep/index.html-
dc.relation.ispartofScientific Reports-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleStalking influenza by vaccination with pre-fusion headless HA mini-stem-
dc.typeArticle-
dc.identifier.emailDoak, SA: sophiev@hku.hk-
dc.identifier.emailChin, WH: alexchin@hku.hk-
dc.identifier.emailPoon, LML: llmpoon@hkucc.hku.hk-
dc.identifier.authorityDoak, SA=rp02141-
dc.identifier.authorityPoon, LML=rp00484-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/srep22666-
dc.identifier.hkuros261178-
dc.identifier.volume6-
dc.identifier.spagearticle no. 22666-
dc.identifier.epagearticle no. 22666-
dc.publisher.placeUnited Kingdom-

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