Modified immunization vectors
Inventors
Pantaleo, Giuseppe • Calandra, Thierry • Harari, Alexandre • Roger, Thierry • Esteban, Mariano • Jacobs, Bertram • Kibler, Karen • Melief, Cornelius • Sekaly, Rafick-Pierre • Haddad, Elias • Tartaglia, James
Assignees
Ippox Foundation • Consejo Superior de Investigaciones Cientificas CSIC • Arizona State University ASU • Arizona State University Downtown Phoenix campus
Publication Number
US-12331307-B2
Publication Date
2025-06-17
Expiration Date
2030-04-29
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Abstract
The disclosure relates to recombinant vectors and methods for using the same. In certain embodiments, the recombinant vectors are immunogenic.
Core Innovation
The invention relates to recombinant vectors, specifically modified viral vectors, and methods of using such vectors in immunological compositions. These recombinant vectors include modifications by deletion and/or insertion of nucleotide sequences encoding immunomodulatory polypeptides and immunogens. The vectors may be derived from vaccinia virus strains such as NYVAC, and can be engineered to express altered immune response profiles by incorporating or deleting specific genes.
The problem addressed is that certain existing recombinant vectors, such as replication-incompetent vaccinia vectors, are insufficient as immunomodulators and their immunological efficacy is limited. There is a need for improved vectors which induce or enhance immune responses, and which may also exhibit improved safety profiles relative to parental vectors. The invention provides modified vectors with changes to host range, virulence, and immunomodulation-related genes to overcome these insufficiencies.
Claims Coverage
The claims disclose five inventive features related to recombinant NYVAC vectors comprising specific polynucleotides and modifications to improve vector characteristics and immunogenicity.
Incorporation of host range genes C7L and K1L into NYVAC genome
Recombinant NYVAC vector including polynucleotides encoding C7L (SEQ ID NO: 17) and K1L (SEQ ID NO: 27) adjacent to one another or alongside additional host range genes such as C1L, C2L, C3L, C4L, C5L, C6L, N1L, N2L, M1L, or M2L within the genome.
Modification to abolish expression of certain polypeptides
One or more modifications in the recombinant NYVAC vector that render the vector unable to express designated polypeptides, including specifically B8R (SEQ ID NO. 1) or B19R (SEQ ID NO. 3).
Deletion of nucleotide sequences for B8R and/or B19R
Recombinant NYVAC vector containing deletion of nucleotide sequences encoding B8R (SEQ ID NO. 2) and/or B19R (SEQ ID NO. 4), modifying the immunomodulatory profile.
Incorporation of ATV eIF2αH gene into NYVAC
The recombinant NYVAC vector further comprising a polynucleotide encoding ATV eIF2αH (SEQ ID NO. 29) to modify host interaction and immune activation.
Inclusion of immunogen-encoding polynucleotides for broad immune targeting
Vectors further including polynucleotides encoding immunogens that direct immune responses against viral, bacterial, parasitic, or tumor target antigens from diverse species and antigen types as specified.
The claims cover recombinant NYVAC vectors with specific host range gene insertions, targeted deletions of immunomodulatory genes, inclusion of heterologous immunomodulator genes such as ATV eIF2αH, and incorporation of diverse immunogen-encoding sequences to improve replication competence, immune response induction, and safety profiles.
Stated Advantages
Modified recombinant vectors induce or enhance an immune response against target antigens.
Vectors may exhibit improved safety profiles compared to parental vectors.
Replication competence restored or optimized in attenuated vaccinia viruses to yield potent immune responses.
Increased pro-inflammatory signal transduction and gene expression are achieved.
Potent T-cell and antibody responses at lower doses are induced by the modified vectors.
Documented Applications
Use of recombinant vectors in immunizing humans and animals against infectious agents, tumor cells, or other antigens by inducing or enhancing immune responses.
Vaccines comprising recombinant vectors expressing clade C HIV immunogens for prophylaxis or therapy of HIV infection.
Vectors used to induce specific immune responses involving dendritic cell maturation, T-cell activation, and cytokine production.
Compositions for immunotherapy or vaccination against viral, bacterial, parasitic, and tumor antigens as listed in the disclosure.
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