Valkenburg, Sophie A and Mallajosyula, Vamsee Aditya V and Li, Olive TW and Chin, Alex WH and Carnell, George and Temperton, Nigel and Varadarajan, Raghavan and Poon, Leo LM (2016) Stalking influenza by vaccination with pre-fusion headless HA mini-stem. In: SCIENTIFIC REPORTS, 6 .
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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: | Journal Article |
|---|---|
| Publication: | SCIENTIFIC REPORTS |
| Publisher: | NATURE PUBLISHING GROUP |
| Additional Information: | Copy right for this article belongs to the NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit |
| Date Deposited: | 02 Apr 2016 05:52 |
| Last Modified: | 02 Apr 2016 05:52 |
| URI: | http://eprints.iisc.ac.in/id/eprint/53577 |
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