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Broecker F, Liu STH, Suntronwong N, et al. A mosaic hemagglutinin-based influenza virus vaccine candidate protects mice from challenge with divergent H3N2 strains. NPJ Vaccines. 2019;4:31doi: 10.1038/s41541-019-0126-4.
Broecker, F., Liu, S. T. H., Suntronwong, N., Sun, W., Bailey, M. J., Nachbagauer, R., Krammer, F., & Palese, P. (2019). A mosaic hemagglutinin-based influenza virus vaccine candidate protects mice from challenge with divergent H3N2 strains. NPJ vaccines, 431. https://doi.org/10.1038/s41541-019-0126-4
Broecker, Felix, et al. "A mosaic hemagglutinin-based influenza virus vaccine candidate protects mice from challenge with divergent H3N2 strains." NPJ vaccines vol. 4 (2019): 31. doi: https://doi.org/10.1038/s41541-019-0126-4
Broecker F, Liu STH, Suntronwong N, Sun W, Bailey MJ, Nachbagauer R, Krammer F, Palese P. A mosaic hemagglutinin-based influenza virus vaccine candidate protects mice from challenge with divergent H3N2 strains. NPJ Vaccines. 2019 Jul 19;4:31. doi: 10.1038/s41541-019-0126-4. eCollection 2019. PMID: 31341648; PMCID: PMC6642189.
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NPJ Vaccines. 2019 Jul 19;4:31. doi: 10.1038/s41541-019-0126-4. eCollection 2019.

A mosaic hemagglutinin-based influenza virus vaccine candidate protects mice from challenge with divergent H3N2 strains.

NPJ vaccines

Felix Broecker, Sean T H Liu, Nungruthai Suntronwong, Weina Sun, Mark J Bailey, Raffael Nachbagauer, Florian Krammer, Peter Palese

Affiliations

  1. 1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY USA.
  2. 2Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  3. 3Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY USA.

PMID: 31341648 PMCID: PMC6642189 DOI: 10.1038/s41541-019-0126-4

Abstract

Current seasonal influenza virus vaccines only provide limited, short-lived protection, and antigenic drift in the hemagglutinin surface glycoprotein necessitates their annual re-formulation and re-administration. To overcome these limitations, universal vaccine strategies that aim at eliciting broadly protective antibodies to conserved epitopes of the hemagglutinin show promise for protecting against diverse and drifted influenza viruses. Here a vaccination strategy that focuses antibody responses to conserved epitopes of the H3 hemagglutinin is described. The approach is based on antigenic silencing of the immunodominant major antigenic sites of an H3 protein from 2014 by replacing them with corresponding sequences of exotic avian hemagglutinins, yielding "mosaic" hemagglutinins. In mice, vaccination with inactivated viruses expressing mosaic hemagglutinins induced highly cross-reactive antibodies against the H3 stalk domain that elicited Fc-mediated effector functions in vitro. In addition, the mosaic viruses elicited head-specific antibodies with neutralizing and hemagglutination-inhibiting activity against recent H3N2 viruses in vitro. Immune sera protected mice from heterologous challenge with viruses carrying H3 proteins from 1968 and 1982, whereas immune sera generated with a seasonal vaccine did not protect. Consequently, the mosaic vaccination approach provides a promising avenue toward a universal influenza virus vaccine.

Keywords: Influenza virus; Preclinical research; Vaccines

Conflict of interest statement

Competing interestsThe Icahn School of Medicine at Mount Sinai has filed patent applications regarding influenza virus vaccines that name F.B., F.K., and P.P. as inventors. The laboratories of F.K. an

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