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

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)

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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: Article
DOI/Identification number: 10.1038/srep22666
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Nigel Temperton
Date Deposited: 08 Mar 2016 13:14 UTC
Last Modified: 29 May 2019 17:04 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/54459 (The current URI for this page, for reference purposes)
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