Plant-derived H7 VLP vaccine elicits protective immune response against H7N9 influenza virus in mice and ferrets

Vaccine. 2015 Nov 17;33(46):6282-9. doi: 10.1016/j.vaccine.2015.09.065. Epub 2015 Oct 2.

Abstract

In March 2013, the Chinese Centre for Disease Control and Prevention confirmed the first reported case of human infection with an avian influenza A H7N9 virus. Infection with this virus often caused severe pneumonia and acute respiratory distress syndrome resulting in a case fatality rate >35%. The risk of pandemic highlighted, once again, the need for a more rapid and scalable vaccine response capability. Here, we describe the rapid (19 days) development of a plant-derived VLP vaccine based on the hemagglutinin sequence of influenza H7N9 A/Hangzhou/1/2013. The immunogenicity of the H7 VLP vaccine was assessed in mice and ferrets after one or two intramuscular dose(s) with and without adjuvant (alum or GLA-SE™). In ferrets, we also measured H7-specific cell-mediated immunity. The mice and ferrets were then challenged with H7N9 A/Anhui/1/2013 influenza virus. A single immunization with the adjuvanted vaccine elicited a strong humoral response and protected mice against an otherwise lethal challenge. Two doses of unadjuvanted vaccine significantly increased humoral response and resulted in 100% protection with significant reduction of clinical signs leading to nearly asymptomatic infections. In ferrets, a single immunization with the alum-adjuvanted H7 VLP vaccine induced strong humoral and CMI responses with antigen-specific activation of CD3(+) T cells. Compared to animals injected with placebo, ferrets vaccinated with alum-adjuvanted vaccine displayed no weight loss during the challenge. Moreover, the vaccination significantly reduced the viral load in lungs and nasal washes 3 days after the infection. This candidate plant-made H7 vaccine therefore induced protective responses after either one adjuvanted or two unadjuvanted doses. Studies are currently ongoing to better characterize the immune response elicited by the plant-derived VLP vaccines. Regardless, these data are very promising for the rapid production of an immunogenic and protective vaccine against this potentially pandemic virus.

Keywords: Ferrets; H7N9; Immunogenicity; Influenza A; Mice; NICOTIANA benthamiana; Plant-made vaccine; Virus-like particle.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Antibodies, Viral / blood
  • Body Weight
  • Disease Models, Animal
  • Female
  • Ferrets
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Immunization Schedule
  • Influenza A Virus, H7N9 Subtype / genetics
  • Influenza A Virus, H7N9 Subtype / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology*
  • Influenza Vaccines / isolation & purification
  • Injections, Intramuscular
  • Lung / virology
  • Male
  • Mice, Inbred BALB C
  • Nasal Cavity / virology
  • Nicotiana
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / prevention & control
  • Placebos / administration & dosage
  • Plants, Genetically Modified
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology*
  • Survival Analysis
  • Vaccines, Virus-Like Particle / administration & dosage
  • Vaccines, Virus-Like Particle / genetics
  • Vaccines, Virus-Like Particle / immunology*
  • Vaccines, Virus-Like Particle / isolation & purification
  • Viral Load

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Placebos
  • Recombinant Proteins
  • Vaccines, Virus-Like Particle
  • hemagglutinin, avian influenza A virus