Computationally optimized broadly reactive antigens for influenza
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsTed M. Ross, Brendan M. Giles
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Abstract
The development of a computationally optimized influenza HA protein that elicits broadly reactive immune response to all H5N1 influenza virus isolates is described. The optimized HA protein was developed through a series of HA protein alignments, and subsequent generation of consensus sequences, for clade 2 H5N1 influenza virus isolates. The final consensus HA amino acid sequence was reverse translated and optimized for expression in mammalian cells. Influenza virus-like particles containing the optimized HA protein are an effective vaccine against H5N1 influenza virus infection in animals.
Claims20
An influenza virus-like particle (VLP) comprising an influenza hemagglutinin (HA) polypeptide, wherein the amino acid sequence of the HA polypeptide is at least 99% identical to SEQ ID NO:
- 2.
A collection of plasmids comprising:
- (i) a plasmid encoding an influenza NA
- (ii) a plasmid encoding an influenza M1;
- and
- (iii) a plasmid encoding a codon-optimized influenza HA, wherein the nucleotide sequence encoding the codon-optimized influenza HA is at least 94% identical to SEQ ID NO:
- 1.
A method of generating an optimized influenza virus polypeptide sequence, comprising:
- (i) obtaining the amino acid sequences of the polypeptide from a group of influenza virus isolates, wherein the influenza virus isolates are from the same subtype;
- (ii) organizing the amino acid sequences of the polypeptide from the group of influenza virus isolates by clade or sub-clade and then by geographical region within each clade or sub-clade;
- (iii) aligning the amino acid sequences within each geographical region to generate primary consensus sequences, wherein each geographic region is represented by a primary consensus sequence;
- (iv) aligning the primary consensus sequences to generate secondary consensus sequences, wherein each clade or sub-clade is represented by a secondary consensus sequence;
- and
- (v) aligning the secondary consensus sequences to generate the optimized influenza virus polypeptide sequence.
Dependencies are inferred from the claim text.