One-shot vaccination with an insect cell-derived low-dose influenza A H7 virus-like particle preparation protects mice against H7N9 challenge

Miriam Klausberger; Monika Wilde; Dieter Palmberger; Rong Hai; Randy A Albrecht; Irina Margine; Ariana Hirsh; Adolfo García-Sastre; Reingard Grabherr; Florian Krammer

doi:10.1016/j.vaccine.2013.11.036

One-shot vaccination with an insect cell-derived low-dose influenza A H7 virus-like particle preparation protects mice against H7N9 challenge

Vaccine. 2014 Jan 9;32(3):355-62. doi: 10.1016/j.vaccine.2013.11.036. Epub 2013 Nov 18.

Authors

Affiliations

¹ Vienna Institute of BioTechnology, University of Natural Resources and Life Sciences, Vienna, Austria.
² Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁴ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁵ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁶ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: Florian.Krammer@mssm.edu.

Abstract

Human infections with a novel influenza A H7N9 subtype virus were reported in China recently. The virus caused severe disease with high mortality rates and it raised concerns over its pandemic potential. Here, we assessed in the mouse model protective efficacy of single immunisations with low vaccine doses of insect cell-derived H7 virus-like particles, consisting of hemagglutinin and matrix protein. Vaccinated mice were fully protected and survived a stringent lethal challenge (100 mLD50) with H7N9, even after a single, unadjuvanted, low vaccine dose (0.03 μg). Serum analysis revealed broad reactivity and hemagglutination inhibition activity across a panel of divergent H7 strains. Moreover, we detected significant levels of cross-reactivity to related group 2 hemagglutinins. These data demonstrate that virus-like particle vaccines have the potential to induce broadly protective immunity against the novel H7N9 virus and a variety of other H7 strains.

Keywords: Baculovirus; Cross-reactivity; H7N9; Influenza; Pandemic; Virus-like particle.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Viral / blood
Cross Reactions
Disease Models, Animal
Female
Hemagglutination Inhibition Tests
Hemagglutinin Glycoproteins, Influenza Virus / administration & dosage
Hemagglutinin Glycoproteins, Influenza Virus / genetics
Hemagglutinin Glycoproteins, Influenza Virus / immunology*
Influenza A Virus, H7N9 Subtype / immunology*
Influenza Vaccines / administration & dosage
Influenza Vaccines / genetics
Influenza Vaccines / immunology*
Mice
Mice, Inbred BALB C
Orthomyxoviridae Infections / prevention & control*
Sf9 Cells
Spodoptera
Survival Analysis
Vaccination / methods*
Vaccines, Virus-Like Particle / administration & dosage
Vaccines, Virus-Like Particle / genetics
Vaccines, Virus-Like Particle / immunology*
Viral Matrix Proteins / administration & dosage
Viral Matrix Proteins / genetics
Viral Matrix Proteins / immunology*

Substances

Antibodies, Viral
Hemagglutinin Glycoproteins, Influenza Virus
Influenza Vaccines
M1 protein, Influenza A virus
Vaccines, Virus-Like Particle
Viral Matrix Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding