Influenza viruses and uses thereof

摘要

Described herein are chimeric influenza virus gene segments and nucleic acid sequences encoding such chimeric influenza virus gene segments. A chimeric influenza virus gene segment described herein comprises packaging signals found in the non-coding and coding regions of one type of influenza virus gene segment and an open reading frame of a different type of influenza virus gene segment or fragment thereof. Also described herein are recombinant influenza viruses comprising two or more chimeric influenza virus gene segments and the use of such viruses in the prevention and/or treatment of influenza virus disease.

主权项

1. A recombinant influenza virus comprising
a) a first chimeric influenza virus gene segment comprising, in 3′ to 5′ order:
(i) a 3′ non-coding region of a first type of influenza virus gene segment;(ii) a 3′ proximal coding region of the first type of influenza virus gene segment, wherein any start codon in the 3′ proximal coding region of the first influenza virus gene segment is mutated;(iii) an open reading frame of a second type of influenza virus gene segment, wherein at least one packaging signal in the 3′ or 5′ proximal nucleotides in the open reading frame is mutated;(iv) a 5′ proximal coding region of the first type of influenza virus gene segment; and(v) a 5′ non-coding region of the first type of influenza virus gene segment; and b) a second chimeric influenza virus gene segment comprising, in 3′ to 5′ order:
(i) a 3′ non-coding region of the second type of influenza virus gene segment;(ii) a 3′ proximal coding region of the second type of influenza virus gene segment, wherein any start codon in the 3′ proximal coding region of the second influenza virus gene segment is mutated;(iii) an open reading frame of the first type of influenza virus gene segment, wherein at least one packaging signal in the 3′ or 5′ proximal nucleotides in the open reading frame is mutated;(iv) a 5′ proximal coding region of the second type of influenza virus gene segment; and(v) a 5′ non-coding region of the second type of influenza virus influenza gene segment.