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EP-3713600-B1 - SYNTHETIC HEMAGGLUTININ AS UNIVERSAL VACCINE AGAINST INFECTION BY TYPE B INFLUENZA VIRUSES (IBV)

EP3713600B1EP 3713600 B1EP3713600 B1EP 3713600B1EP-3713600-B1

Inventors

  • LI, XUGUANG
  • VAN DOMSELAAR, GARY
  • ZETNER, Adrian

Dates

Publication Date
20260506
Application Date
20181116

Claims (5)

  1. An adenoviral vector encoding a protein as set forth in SEQ ID No:1 or SEQ ID No:2 for use in a method of immunizing an individual against influenza virus B, wherein the adenoviral vector is administered intranasally.
  2. The adenoviral vector for use according to claim 1, wherein the individual is at significant risk of being infected by influenza virus B.
  3. The adenoviral vector for use according to claim 1, wherein the individual is at risk of suffering moderate to severe complications from influenza.
  4. The adenoviral vector for use according to claim 1, wherein the individual is at a higher risk of being exposed to influenza virus B than the general population.
  5. The adenoviral vector for use according to claim 1, wherein the individual is a young child, an adult aged 65 years or older, a pregnant woman, an individual with asthma or an individual with chronic lung disease, chronic heart disease or another chronic medical condition.

Description

BACKGROUND OF THE INVENTION Influenza can infect as much as 5-15% of the world population, resulting in 3-5 million cases of severe illness and up to 500,000 deaths per year. In the US alone, flu epidemics lead to approximately 300,000 influenza-related hospital admissions and 36,000 influenza related deaths annually in addition to an estimated cost of $12 billion per year. Current seasonal influenza vaccines are produced with strains recommended by the World Health Organization about 9-12 months ahead of the targeted season. The vaccines typically contain two type A influenza strains and one type B influenza strain, which are predicted to be the most likely strains to cause the upcoming flu epidemic. However, there are inherent disadvantages associated with the preparation of conventional influenza vaccines such as the uncertainty of the actual circulating strain, the need for annual updating of the manufacturing process and preparation of reagents for vaccine lot release. Clearly, the drawbacks associated with traditional vaccine preparation would be drastically exacerbated in the event of an outbreak of pandemic influenza, given a perceivably much shortened timeframe available for the production of prophylactic vaccines for global needs. All these problems concerning the influenza vaccines are largely due to one single biological property of the influenza virus itself, i.e. the constant mutations of the virus surface proteins hemagglutinin (HA) and neuraminidase (NA). The make-up of the main influenza antigen, hemagglutinin (HA), changes constantly in circulating strains of both influenza type A virus and influenza type B virus (IBV). IBV is responsible for up to a quarter of annual influenza infections, on an annual basis. There remains a need in the art for therapies and prevention strategies that can be used to prevent a wide range of infection by various influenza strains. The international patent application No. WO 2013/079473 A1 discloses influenza hemagglutinin stem domain polypeptides, methods for providing hemagglutinin stem domain polypeptides, compositions comprising the same, vaccines comprising the same and methods of their use, in particular in the detection, prevention and/or treatment of influenza. The international patent application No. WO 2010/117786 A1 discloses influenza hemagglutinin stem domain polypeptides, compositions comprising the same, vaccines comprising the same and methods of their use. SUMMARY OF THE INVENTION According to an aspect of the invention, an adenoviral vector encoding a protein as set forth in SEQ ID No:1 or SEQ ID No:2 for use in a method of immunizing an individual against influenza virus B as specified in claim 1 is provided. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a schematic diagram of the main sequence variants in Influenza Virus B stem subunit.Figure 2 is a bar graph showing the number of strains of Influenza Virus B having 0-7 amino acids different from the sHA stem protein.Figure 3 shows the structure of the two vaccine constructs: rAd-HBHA2F and rAd-HBHA2FCD4QL These genes were cloned into rAd vector under the control of CMV promoter. "S" denotes secretion signal, "HB" denotes the HA2 of IBV HA, "F" denotes "trimerizing motif".Figure 4 shows antibody titer analysis. Panels A and B show after intra-nasal administration of the vaccine with CD40 ligand, the antibodies titres are higher than the vector controls. Panels C & D shows the same except the administration route is sub-cutaneous.Figure 5 shows survival results of vaccinated animals and controls post viral challenge.Figure 6 shows pathological changes in lungs from animals post virus challenging. Panel A is a sample of lung tissue from an animal without vaccine (vector control). Panel B is a sample of lung tissue from the vaccinated group. DESCRIPTION OF THE PREFERRED EMBODIMENTS Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are now described. The practice of the present invention will employ, unless otherwise indicated, conventional methods of chemistry, biochemistry, recombinant DNA techniques and immunology, within the skill of the art. Such techniques are explained fully in the literature. See, e.g., Fundamental Virology, 2nd Edition, vol. I & II (B. N. Fields and D. M. Knipe, eds.); Handbook of Experimental Immunology, Vols. I-IV (D. M. Weir and C. C. Blackwell eds., Blackwell Scientific Publications); T. E. Creighton, Proteins: Structures and Molecular Properties (W. H. Freeman and Company, 1993); A. L. Lehninger, Biochemistry (Worth Publishers, Inc., current addition); Sambrook, et al., Molecular Cloning: A Laboratory Manual (2nd Edition, 1989); Methods In Enzymolog