Peptides for inducing heterosubtypic influenza T cell responses
Inventors
HOFT, Daniel F. • EICKHOFF, Christopher S. • DE GROOT, Annie
Assignees
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Publication Number
US-12247053-B2
Publication Date
2025-03-11
Expiration Date
Abstract
The present invention provides compositions and methods for generation of an anti-influenza immune response. In particular, conserved T cell epitopes within matrix protein and nucleoprotein components of influenza virus have been identified and further screened for those structures that will bind either or both of HLA I and II molecules. Methods for vaccinating subjects with formulations of such peptides for the treatment or prevention of influenza infection also are described.
Core Innovation
The invention relates to an influenza vaccine strategy that uses T-cell epitopes derived from influenza A matrix (M1/M2) and nucleoprotein (NP) proteins. The approach identifies pan-HLA-DR class II immunogenic consensus sequences and HLA-A2 supertype class I epitopes intended to bind HLA I/II while avoiding significant homology to human sequences. The resulting epitope sets are described as immunogenic.
The disclosed vaccine components include synthetic peptides, peptide pools, peptide-fused constructs, and DNA vaccines encoding optimized minigenes and related epitope sets, including SEQ ID NOs: 57 and 58. The peptides and compositions are described as being formulated, including lyophilized compositions, and the nucleic acid constructs are described as encoding the peptides.
The invention is further supported by reported immunogenicity and protective activity in HLA transgenic mouse models and human PBMC assays. The vaccines and epitopes are reported to provide broadly protective or heterotypic protection against H1N1 and H3N2 influenza challenges, including reduced viral burden and improved survival, without relying on neutralizing antibody epitopes.
Claims Coverage
The independent claim is directed to a peptide having the sequence of SEQ ID NO: 57 or 58. Dependent claims further define a lyophilized peptide, a nucleic acid encoding the peptide, and administration of the nucleic acid to induce an immune response in a subject. This yields four inventive features centered on the peptide sequence, formulation state, and nucleic-acid immunization context.
Peptide comprising the sequence of SEQ ID NO: 57 or 58
A peptide comprising the sequence of SEQ ID NO: 57 or 58.
Lyophilized peptide
The peptide is lyophilized.
Nucleic acid encoding the peptide
A nucleic acid that encodes the peptide described as comprising the sequence of SEQ ID NO: 57 or 58.
Administering the nucleic acid to induce an immune response
A method for inducing an immune response in a subject by administering the nucleic acid to the subject.
Overall, the claim coverage focuses on the specific peptide sequences of SEQ ID NO: 57 or 58, optionally in lyophilized form, and on nucleic acids encoding these peptides, where administration of the nucleic acid is used to induce an immune response in a subject.
Stated Advantages
Improved survival in reported challenges.
Reduced viral burden in reported challenges.
Broadly protective or heterotypic protection against H1N1 and H3N2 influenza challenges.
Immunogenicity of the disclosed vaccine and epitope components is reported.
Protection is reported without relying on neutralizing antibody epitopes.
Documented Applications
Use of the disclosed influenza vaccine and epitope components in HLA transgenic mouse models and human PBMC assays, where reported immunogenicity and protective or heterotypic outcomes are observed against H1N1 and H3N2 influenza challenges.
Delivery contexts described include injection or inhalation for the vaccine components.
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