Novel influenza antigens

Abstract

The present invention relates to novel influenza antigens, novel immunogenic or vaccine compositions, as well as to uses of and to methods for producing said antigens and compositions. In particular, the invention relates to recombinant forms of hemagglutinin (HA) and their use in vaccine compositions for the prevention of influenza virus infections.

1 - 27 . (canceled) 
     
     
         28 . A method for producing a recombinant influenza virus hemagglutinin (HA) antigen comprising the extracellular domain of HA or an immunogenic portion thereof, a hydrophobic signal and a heterologous trimerisation domain comprising expressing a polynucleotide encoding said recombinant influenza virus hemagglutinin (HA) antigen in a eukaryotic cell, such as a mammalian cell, e.g. a CHO cell, or an insect cell, optionally further comprising purifying/isolating the recombinant HA from the eukaryotic cell. 
     
     
         29 . A method for prevention and/or vaccination against influenza disease, comprising the administration a recombinant influenza virus hemagglutinin (HA) antigen comprising the extracellular domain of HA or an immunogenic portion thereof, followed by a hydrophobic signal, followed by a heterologous trimerisation domain to a person in need thereof. 
     
     
         30 . The method of  claim 29 , wherein less than 15 micrograms of hemagglutinin are administered per dose. 
     
     
         31 . The method of  claim 30 , wherein 3.75 to 10 micrograms of hemagglutinin are administered per dose. 
     
     
         32 . The method of  claim 29 , wherein the hydrophobic signal comprises a stretch of at least 5 hydrophobic amino acids. 
     
     
         33 . The method of  claim 29 , wherein the hydrophobic signal is an HA transmembrane domain. 
     
     
         34 . The method of  claim 29 , wherein the HA antigen lacks the intracellular domain of influenza hemagglutinin. 
     
     
         35 . The method of  claim 29 , wherein the hemagglutinin is not full length hemagglutinin. 
     
     
         36 . The method of  claim 29 , wherein the recombinant HA antigen forms rosette structures in vivo or in vitro. 
     
     
         37 . The method of  claim 29 , which additionally comprises a cleavable linkage. 
     
     
         38 . The method of  claim 29 , wherein the hemagglutinin is from an H1, H2, H3, H5, H7 or H9 strain. 
     
     
         39 . The method of  claim 29 , wherein the HA transmembrane is heterologous to the extracellular domain of said HA. 
     
     
         40 . The method of  claim 29 , wherein i) the HA ECD consists of or comprises SEQ ID NO:
 7, ii) the HA TMD consists of or comprises SEQ ID NO: 5 or a fragment or derivative of this sequence that retains the ability to orientate HA trimers into rosette structures and maintains the immunogenicity of HA and/or iii) the trimerisation domain consists of or comprises SEQ ID NO: 9 or a derivative of this sequence that maintains the ability to induce rHA monomers to form trimers.   
     
     
         41 . The method of  claim 29 , wherein i) the HA ECD consists of or comprises SEQ ID NO:
 7, ii) the HA TMD consists of or comprises SEQ ID NO:5 and iii) the trimerisation domain consists of or comprises SEQ ID NO: 9.   
     
     
         42 . The method of  claim 29 , wherein the HA antigen comprises the sequence of SEQ ID NO:1. 
     
     
         43 . The method of  claim 29 , wherein the hemagglutinin lacks the HA stalk, or part of the stalk. 
     
     
         44 . The method of  claim 29 , comprising administration of an immunogenic composition comprising the hemagglutinin (HA) antigen and a pharmaceutically-acceptable carrier. 
     
     
         45 . The method of  claim 44 , wherein the immunogenic composition further comprises an adjuvant. 
     
     
         46 . The method of  claim 45 , wherein the adjuvant is an oil-in-water emulsion adjuvant. 
     
     
         47 . The method of  claim 44 , wherein the composition is multivalent or monovalent.