Human interleukin-2 (IL-2) muteins or variants thereof are provided. In particular, provided are IL-2 muteins that have an increased binding capacity for IL-2Rβ receptor as compared to wild-type IL-2 for use in combination therapies with anti-PD-1 antibodies for the treatment of cancer. Also provided are pharmaceutical compositions that include such anti-PD-1 antibodies and the disclosed IL-2 muteins.

The present invention relates to oncolytic vaccinia viruses which have been modified to promote anti-tumor immunity and/or reduce host immunity and/or antibody response against the virus. It is based, at least in part, on the discovery that oncolytic vaccinia virus (i) bearing a genome deletion of a gene that reduces T cell immunity (interleukin-18 binding protein); (ii) treated with a sialidase enzyme which is believed to reduce TLR2 activation and therefore the antibody response; (iii) carrying a gene that enhances cytotoxic T lymphocyte induction (e.g., TRIF) and/or (iv) reduces tumor myeloid-derived suppressor cells by reducing prostaglandin E2 reduces tumor growth. Accordingly, the present invention provides for immunooncolytic vaccinia viruses and methods of using them in the treatment of cancers.

The present invention generally relates to a process for designing a recombinant poxvirus for a therapeutic vaccine, i.e. personalized cancer vaccine, said recombinant poxvirus comprising one or more expression cassettes, each for expression of a fusion of a plurality of peptides, i.e. neopeptides, characterized in that it comprises performing by processing means (11) of a server (1) the steps of : (a) selecting a first subset of candidate peptides, wherein said peptides present transmembrane scores below a TMS threshold; b) determining an optimal distribution of the candidate peptides from said first subset to the expression cassette(s) among a plurality of possible distributions, wherein said optimal distribution presents, if there are at least two expression cassettes, the lowest range between the hydropathy scores of at least two expression cassettes; (c) for each expression cassette, determining an optimal slot allocation of the candidate peptides as function of cassette slot occupancy rule so as to select the peptide fusion with the lowest TM score; (d) determining a DNA transfer sequence comprising the nucleotide sequence of the one or more expression cassette(s) for generation of said recombinant poxvirus.

The disclosure provides, inter alia, methods and materials involved in treating cancer using a p53 vaccine in combination with a PD-1 pathway inhibitor.

The invention refers to new immuno-modulated replication-efficient Vaccinia virus strain (IOVA) and its derivatives for the use in medicine.

This disclosure relates to methods of promoting immune responses against coronavirus, such as SARS-CoV-2, and compositions related thereto. In certain embodiments, this disclosure relates to methods of vaccinating for coronavirus comprising administering to the subject a composition disclosed herein. In certain embodiments, the composition comprises a recombinant virus such as recombinant MVA that encodes a coronavirus spike protein. In certain embodiments, the coronavirus spike protein comprises a proline mutation at position 986. In certain embodiments, the coronavirus spike protein comprises a proline mutation at position 987.

Disclosed herein are methods and compositions related to therapy for cancer. More specifically, the disclosed methods and compositions are related to the use of smallpox vaccine to induce an effective anti-tumor immune response.

The present invention relates to the development and manufacturing of viral vaccines. In particular, the invention relates to the field of industrial production of viral vectors and vaccines, more in particular to the use of avian embryonic stem cells, preferably the EBx® cell line derived from duck embryonic stem cells, for the production of viral vectors and viruses. The invention is particularly useful for the industrial production of viral vaccines to prevent viral infection of humans and animals.

The present disclosure provides, in part, a priming and boosting vector-based platform to develop vaccines against pathogens that is tailored to elicit a broad T cell response targeting conserved viral epitopes. The universal vaccines are prepared against an immunogen of an infectious pathogenic organism selected from a virus, a bacteria, a fungus or a protozoan comprising at least one ribonucleic acid (RNA) polynucleotide comprising an open reading frame encoding at least one polypeptide antigen or an immunogenic fragment thereof, wherein the polypeptide antigen, or the immunogenic fragment thereof, comprises a conserved internal protein that is enriched in CD8+ T cell recognition antigens. The effectiveness of the priming and boosting platform is tested in a humanized mouse model comprising a fully functional human immune system.

Disclosed herein are methods and compositions related to the treatment, prevention, and/or amelioration of cancer in a subject in need thereof. In particular aspects, the present technology relates to the use of genetically engineered or recombinant poxviruses, including a modified vaccinia Ankara (MVA) virus comprising a deletion of E3L (MVAΔE3L) engineered to express OX40L (MVAΔE3L-OX40L), an MVA virus comprising a deletion of C7L (MVAΔC7L) engineered to express OX40L (MVAΔC7L-OX40L), a MVAΔC7L engineered to express OX40L and human Fms-like tyrosine kinase 3 ligand (hFlt3L) (MVAΔC7L-hFlt3L-OX40L), an MVA comprising a deletion of E5R (MVAΔE5R), a vaccinia virus comprising a deletion of C7L (VACVΔC7L) engineered to express OX40L (VACVΔC7L-OX40L), a VACVΔC7L engineered to express both OX40L and hFlt3L (VACVΔC7L-hFlt3L-OX40L), a VACV comprising a deletion of E5R (VACVΔE5R), a myxoma virus (MYXV) comprising a deletion of M31R (MYXVΔM31R), or combinations thereof, alone or in combination with other agents, as an oncolytic and immunotherapeutic composition.