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Sci Rep. 2016 Mar 7;6:22666. doi: 10.1038/srep22666.

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

Author information

1
HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
2
Center of Influenza Research and School of Public Health, The University of Hong Kong, Hong Kong.
3
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
4
Viral Pseudotype Unit, School of Pharmacy, University of Kent, Kent, United Kingdom.

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.

PMID:
26947245
PMCID:
PMC4780079
DOI:
10.1038/srep22666
[Indexed for MEDLINE]
Free PMC Article

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