The present invention provides a modified influenza virus wherein the RNA of the haemagglutinin gene has been modified such that the haemagglutinin signal sequence is not expressed and the virus produces a haemagglutinin protein that lacks a functional signal sequence. The invention further provides composition comprising the modified virus and uses of the modified virus.
1. A modified influenza virus wherein the RNA of the haemagglutinin gene has been modified such that the haemagglutinin signal sequence is not expressed and the virus produces a haemagglutinin protein that lacks a functional signal sequence.
2. The modified virus of claim 1 wherein the RNA is modified such that the RNA corresponding to the haemagglutinin signal sequence has at least about 60% or more sequence homology with the wild type haemagglutinin signal sequence RNA.
3. The modified virus of claim 1 wherein the influenza virus is type A.
4. The modified virus of claim 1 comprising i) a mutation in the original start codon for translation of the haemagglutinin gene such that it is no longer a start codon; and ii) the introduction of a new start codon to drive translation of the haemagglutinin gene just after the signal sequence.
5. The modified virus of claim 1 , wherein the RNA of the haemagglutinin gene comprises one or more of the following:
i) mutation of the first nucleotide of a start codon of a haemagglutinin gene and/or mutation of the second nucleotide of a start codon of a haemagglutinin gene such that the start codon is removed;
ii) deletion of the base at the end of the signal sequence of a haemagglutinin gene;
iii) insertion of a Kozak sequence in the place of the base at the end of the signal sequence of a haemagglutinin gene;
iv) mutations of one or more of nucleotides 1063, 1064 and 1065 of a haemagglutinin gene to remove the cleavage site.
6. A method of preparing a modified influenza virus according to claim 1 comprising i) providing a host cell that expresses haemagglutinin with a signal sequence from a eukaryotic mRNA; and ii) providing the viral genomic nucleic acid segments for the modified virus under conditions whereby the segments are packaged into a viral particle.
7. An immunogenic composition comprising a modified influenza virus according to claim 1 .
8. The immunogenic composition of claim 7 wherein the composition is capable of eliciting an immune response when administered to a human or non-human animal.
9. The immunogenic composition of claim 7 wherein the composition is suitable for intranasal administration.
10. The immunogenic composition of claim 7 wherein the composition is effective against one or more influenza strains.
11. The immunogenic composition of claim 7 comprising a further one or more antigens, in addition to the modified virus.
12. The immunogenic composition of claim 7 suitable for use as a prophylactic or a therapeutic vaccine directed to the influenza virus.
13. The immunogenic composition of claim 7 suitable for use as part of a prime boost vaccination regimen.
14. A pharmaceutical composition comprising a virus of claim 1 or a composition of claim 7 and a pharmaceutically acceptable carrier or excipient.
15. A composition comprising a modified influenza virus according to claim 1 capable of generating an immune response to influenza.
16. The composition of claim 15 wherein the immune response is prophylactic or therapeutic.
17. A method of protecting a human or non-human animal from the effects of infection by the influenza virus comprising administering to the human or non-human animal a virus according to claim 1 or a composition according to claim 7 .
18. A method for raising an immune response in a human or non-human animal comprising administering a pharmaceutical composition according to claim 14 to the human or non-human animal.
19. A kit for use in inducing an immune response in an organism, comprising an immunogenic composition according to claim 7 and instructions relating to administration.