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- Publisher Website: 10.1038/srep22666
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Conference Paper: Stalking influenza by vaccination with pre-fusion headless HA mini-stem
Title | Stalking influenza by vaccination with pre-fusion headless HA mini-stem |
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Authors | |
Issue Date | 2016 |
Publisher | Nature 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? |
Abstract | Inaccuracies 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 Identifier | http://hdl.handle.net/10722/230500 |
ISSN | 2023 Impact Factor: 3.8 2023 SCImago Journal Rankings: 0.900 |
ISI Accession Number ID | |
Grants |
DC Field | Value | Language |
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dc.contributor.author | Doak, SA | - |
dc.contributor.author | Mallajosyula, VV | - |
dc.contributor.author | Li, OTW | - |
dc.contributor.author | Chin, WH | - |
dc.contributor.author | Carnell, G | - |
dc.contributor.author | Temperton, N | - |
dc.contributor.author | Varadarajan, R | - |
dc.contributor.author | Poon, LML | - |
dc.date.accessioned | 2016-08-23T14:17:24Z | - |
dc.date.available | 2016-08-23T14:17:24Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | The 2016 Lorne Infection and Immunity Conference, Lorne VIC., Australia, 17-19 February 2016. In Scientific Reports, 2016, article no. 22666 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | http://hdl.handle.net/10722/230500 | - |
dc.description.abstract | Inaccuracies 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.language | eng | - |
dc.publisher | Nature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/srep/index.html | - |
dc.relation.ispartof | Scientific Reports | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | Stalking influenza by vaccination with pre-fusion headless HA mini-stem | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Doak, SA: sophiev@hku.hk | - |
dc.identifier.email | Chin, WH: alexchin@hku.hk | - |
dc.identifier.email | Poon, LML: llmpoon@hkucc.hku.hk | - |
dc.identifier.authority | Doak, SA=rp02141 | - |
dc.identifier.authority | Poon, LML=rp00484 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1038/srep22666 | - |
dc.identifier.scopus | eid_2-s2.0-84960448072 | - |
dc.identifier.hkuros | 261178 | - |
dc.identifier.hkuros | 261335 | - |
dc.identifier.hkuros | 261336 | - |
dc.identifier.volume | 6 | - |
dc.identifier.spage | article no. 22666 | - |
dc.identifier.epage | article no. 22666 | - |
dc.identifier.isi | WOS:000371407500002 | - |
dc.publisher.place | United Kingdom | - |
dc.relation.project | Control of Pandemic and Inter-pandemic Influenza | - |
dc.identifier.issnl | 2045-2322 | - |