4.7 Article

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

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SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -

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NATURE PUBLISHING GROUP
DOI: 10.1038/srep22666

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  1. Areas of Excellence Scheme of the University Grants Committee [AoE/M-12/06]
  2. NIAID contract [HHSN272201400006C]
  3. GRF [HKU 776213M]
  4. Department of Biotechnology, Government of India
  5. Council of Scientific and Industrial Research, Government of India

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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.

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