Valkenburg, Sophie A, Mallajosyula, V Vamsee Aditya, Li, Olive T W, Chin, Alex W H, Carnell, George, Temperton, Nigel J., Varadarajan, Raghavan, Poon, Leo L M (2016) Stalking influenza by vaccination with pre-fusion headless HA mini-stem. Scientific reports, 6 . pp. 22666-22676. ISSN 2045-2322. E-ISSN 2045-2322. (doi:10.1038/srep22666) (KAR id:54459)
PDF
Publisher pdf
Language: English
This work is licensed under a Creative Commons Attribution 4.0 International License.
|
|
Download this file (PDF/1MB) |
Preview |
Request a format suitable for use with assistive technology e.g. a screenreader | |
Official URL: http://dx.doi.org/10.1038/srep22666 |
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 indudced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity.
Item Type: | Article |
---|---|
DOI/Identification number: | 10.1038/srep22666 |
Subjects: | Q Science > QR Microbiology > QR355 Virology |
Divisions: | Divisions > Division of Natural Sciences > Medway School of Pharmacy |
Depositing User: | Nigel Temperton |
Date Deposited: | 08 Mar 2016 13:14 UTC |
Last Modified: | 09 Dec 2022 05:13 UTC |
Resource URI: | https://kar.kent.ac.uk/id/eprint/54459 (The current URI for this page, for reference purposes) |
- Link to SensusAccess
- Export to:
- RefWorks
- EPrints3 XML
- BibTeX
- CSV
- Depositors only (login required):