File Download
  Links for fulltext
     (May Require Subscription)

Conference Paper: 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
The 2016 Lorne Infection and Immunity Conference, Lorne VIC., Australia, 17-19 February 2016. In Scientific Reports, 2016, article no. 22666 How to Cite?
AbstractAntigenic drift of the HA head necessitates seasonal influenza vaccination, therefore in a bid to develop a universal vaccine, we adopted the approach of protein minimization of the HA protein to focus the antibody response towards the functionally conserved epitopes of the HA stem, using a H5 and H1 based vaccine in a mouse model. The H5 HA mini-stem protein refolds as a trimer, in a highly stable pre-fusion conformation representing the native conformation of the HA stem. The HA mini-stem is biochemically stable under diverse stress conditions, rendering the vaccine compatible for bulk production from E. Coli and pandemic stockpiling. Due to the ideal conformational nature of our HA mini-stem, antibodies elicited by the vaccine competed with other broadly neutralizing stem-specific antibodies (CR6261, F10 and FI6v3). Vaccine stem-specific antibodies were broadly reactive against HA proteins, binding with high affinity. Ultimately, vaccination of mice with the H1 and H5 HA mini-stem resulted in significant protection from morbidity and mortality against challenge with homologous and heterologous influenza viruses, including group 2 influenza, H3N2 challenge. Ours study is the first report of a Group 1 HA-stem vaccine showing Group 2 protection. Passive immune sera transfer demonstrated protection was mediated by vaccine stem-specific antibodies. Virus micro-neutralization was observed by vaccine immune sera for H1N1, H7N7 and H3N2 viruses, but not H5N1 viruses, despite clear protection in vaccinated and passive transfer experiments for H5N1 viruses. This raises important issues for the role of stem-specific antibodies, and whether neutralization is a requisite for board spectrum protection. We believe that this observation will provide critical research directions for developing novel universal influenza vaccines.
DescriptionOpen Access Article
Persistent Identifierhttp://hdl.handle.net/10722/230540
ISSN
2015 Impact Factor: 5.228
2015 SCImago Journal Rankings: 2.073

 

DC FieldValueLanguage
dc.contributor.authorValkenburg, SA-
dc.contributor.authorMallajosyula, VA-
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.accessioned2016-08-23T14:17:38Z-
dc.date.available2016-08-23T14:17:38Z-
dc.date.issued2016-
dc.identifier.citationThe 2016 Lorne Infection and Immunity Conference, Lorne VIC., Australia, 17-19 February 2016. In Scientific Reports, 2016, article no. 22666-
dc.identifier.issn2045-2322-
dc.identifier.urihttp://hdl.handle.net/10722/230540-
dc.descriptionOpen Access Article-
dc.description.abstractAntigenic drift of the HA head necessitates seasonal influenza vaccination, therefore in a bid to develop a universal vaccine, we adopted the approach of protein minimization of the HA protein to focus the antibody response towards the functionally conserved epitopes of the HA stem, using a H5 and H1 based vaccine in a mouse model. The H5 HA mini-stem protein refolds as a trimer, in a highly stable pre-fusion conformation representing the native conformation of the HA stem. The HA mini-stem is biochemically stable under diverse stress conditions, rendering the vaccine compatible for bulk production from E. Coli and pandemic stockpiling. Due to the ideal conformational nature of our HA mini-stem, antibodies elicited by the vaccine competed with other broadly neutralizing stem-specific antibodies (CR6261, F10 and FI6v3). Vaccine stem-specific antibodies were broadly reactive against HA proteins, binding with high affinity. Ultimately, vaccination of mice with the H1 and H5 HA mini-stem resulted in significant protection from morbidity and mortality against challenge with homologous and heterologous influenza viruses, including group 2 influenza, H3N2 challenge. Ours study is the first report of a Group 1 HA-stem vaccine showing Group 2 protection. Passive immune sera transfer demonstrated protection was mediated by vaccine stem-specific antibodies. Virus micro-neutralization was observed by vaccine immune sera for H1N1, H7N7 and H3N2 viruses, but not H5N1 viruses, despite clear protection in vaccinated and passive transfer experiments for H5N1 viruses. This raises important issues for the role of stem-specific antibodies, and whether neutralization is a requisite for board spectrum protection. We believe that this observation will provide critical research directions for developing novel universal influenza vaccines.-
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.titleStalking influenza by vaccination with pre-fusion headless HA mini-stem-
dc.typeConference_Paper-
dc.identifier.emailLi, OTW: litwo@hku.hk-
dc.identifier.emailChin, WH: alexchin@hku.hk-
dc.identifier.emailPoon, LML: llmpoon@hkucc.hku.hk-
dc.identifier.authorityPoon, LML=rp00484-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1038/srep22666-
dc.identifier.hkuros261335-
dc.identifier.hkuros261336-
dc.publisher.placeUnited Kingdom-
dc.customcontrol.immutablesml 160907-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats