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

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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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: Journal Article
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
Depositing User: Id for Latest eprints
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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