Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10350285-B2
Publication Date
2019-07-16
Expiration Date
Abstract
The invention relates to a protein comprising a plurality of conserved peptide sequences, or variants thereof, wherein at least one of the conserved sequences is conserved across all four dengue virus serotypes DENV-1, DENV-2, DENV-3 and DENV-4, and wherein the conserved sequences comprise at least part of a sequence of one or more non-structural proteins of the dengue virus serotypes. The invention further relates to associated peptides, compositions, nucleic acids, viral vectors, virus-like particles, use, prime boost vaccination kits, agents and methods.
Core Innovation
The invention relates to a dengue vaccine concept that uses immunogenic, non-structural antigen-derived conserved peptide sequences spanning dengue virus types DENV-1, DENV-2, DENV-3 and DENV-4. The conserved peptide sequences are used to generate T-cell responses directed to non-structural proteins (NS1, NS2, NS3, NS4 and NS5), and the vaccine design is intended to reduce antibody-mediated enhancement risk associated with dengue immunity.
Conserved peptide sequences are selected based on conservation criteria and a sliding-window bioinformatics approach. The disclosure presents multiple conserved-sequence constructs (NSALL1 to NSALL4) and includes epitope variants among the conserved sequences, and the constructs may be assembled as fusion proteins, including fusion protein variants defined by identity thresholds such as at least 80% identity.
The vaccine is provided in multiple formats, including nucleic acids encoding fusion proteins and non-replicating viral vectors, as well as virus-like particles and prime-boost vaccination kits. The disclosure also discusses avoiding false junction epitopes by reordering conserved peptide sequences between prime and boost while maintaining the use of conserved peptide sequences across the dengue virus types.
Claims Coverage
The independent claim covers a nucleic acid encoding a fusion protein composed of multiple conserved peptide sequences (SEQ ID NOs 4 to 114) with variants meeting a sequence identity threshold of at least 80% identity. Dependent inventive features further add specific fusion protein content, an immunological function, viral-vector delivery, and prime/boost vaccination where peptide sequence order differs between prime and boost.
Fusion-protein encoding nucleic acid with multiple conserved peptide sequences
A nucleic acid comprising a sequence encoding a fusion protein, wherein the fusion protein comprises peptide sequences of SEQ ID NO: 4 through SEQ ID NO: 114, including listed SEQ ID NOs and variants with at least 80% identity with the peptide sequences.
Specific fusion protein content with identity threshold
The nucleic acid encodes a fusion protein that includes peptide sequences of SEQ ID NO: 72 or a variant with at least 80% identity to the peptide sequences of SEQ ID NO: 72.
Induction of T-cell mediated immunity
The nucleic acid activates T-cell mediated immunity in a subject.
Viral vector comprising the encoding nucleic acid
A viral vector comprising the nucleic acid.
Prevention, treatment, or inhibition of dengue virus infection
A method that prevents or treats or inhibits dengue virus infection in a subject by administering the nucleic acid.
Prime/boost vaccination with altered conserved peptide sequence order
A method for preventing dengue-virus-associated disease or treating or inhibiting a dengue viral infection by administering a prime nucleic-acid vaccine followed by a boost nucleic-acid vaccine, wherein the encoded peptide sequence order in the boost differs from that in the prime.
Overall, the claims concentrate on nucleic acids encoding multi-peptide fusion proteins built from conserved peptide sequences with variant identity requirements, coupled with activation of T-cell mediated immunity. Coverage extends to viral-vector formats and dengue prevention or treatment use, including a prime/boost strategy where the order of encoded peptide sequences differs between prime and boost.
Stated Advantages
Reduces antibody-mediated enhancement risk.
Induces T-cell responses directed to dengue virus non-structural proteins.
Documented Applications
Dengue vaccine use to prevent or treat dengue virus infection in a subject, including prime-boost vaccination where the peptide sequence order in the boost differs from that in the prime.
Methods for preventing dengue-virus-associated disease or treating or inhibiting a dengue viral infection by administering a prime nucleic-acid vaccine followed by a boost nucleic-acid vaccine.
Preclinical immunogenicity evidence in mice using ex vivo IFN-γ ELISPOT to show increased T-cell responses after prime-boost with adenoviral and/or MVA vectors.
Interested in licensing this patent?