The present disclosure discloses a whole avian-origin reverse genetic manipulation system and its use in producing a recombinant H7N9 avian influenza vaccine. The whole avian-origin reverse genetic manipulation system is an eight-plasmid reverse genetic manipulation system based on H5N2 subtype avian influenza D7 virus strain, which is comprised of 8 recombinant plasmids respectively containing PB2, PB1, PA, HA, NP, NA, M and NS gene fragments derived from H5N2 subtype avian influenza D7 virus strain. The genome of the recombinant H7N9 subtype avian influenza vaccine of the present disclosure is comprised of an NA gene and a modified HA gene derived from a highly pathogenic H7N9 subtype avian influenza virus strain, as well as PB2, PB1, PA, NP, M and NS genes derived from H5N2 subtype avian influenza D7 virus strain.

Provided herein are, inter alia, compositions including recombinant oncolytic herpes simplex viruses that express SARS-CoV spike (S) protein and viral vectors including nucleic acid sequences encoding SARS-CoV S protein. The compositions are useful for eliciting antibodies to SARS-CoV. The compositions are contemplated to be particularly useful for methods of treating and preventing SARS coronavirus infections in cancer patients.

Disclosed herein are nucleic acid molecules encoding a Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) spike antigen, SARS-CoV-2 spike antigens, immunogenic compositions, and vaccines and their use in inducing immune responses and protecting against or treating a SARS-CoV-2 infection in a subject.

Viruses, and particularly genetically engineered, replication deficient viruses such as adenoviruses, poxviruses, MVA viruses, and baculoviruses which encode one or more antigens of interest, such as TB, malarial, and HIV antigens, are spray dried with a mannitol-cyclodextrin-trehalose-dextran (MCTD) to form a powder where the viability of the viruses are maintained at a suitable level for mass vaccinations after spray drying, and where the viability of the viruses are maintained at suitable level over a period of storage time, even in the presence of humidity.

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 invention provides hybrid and recombinant phagemid vectors for expressing a transgene in a target cell transduced with the vector. A recombinant phagemid particle comprises at least one transgene expression cassette which encodes an agent which exerts a biological effect on the target cell, characterised in that the phagemid particle comprises a genome which lacks at least 50% of its bacteriophage genome. The invention extends to the use of such phagemid expression systems as a research tool, and for the delivery of transgenes in a variety of gene therapy applications, DNA and/or peptide vaccine delivery and imaging techniques. The invention extends to in vitro, in vivo or in situ methods for producing viral vectors, such as recombinant adeno-associated viruses (rAAV) or lentivirus vectors (rLV), and to genetic constructs used in such methods.

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

Disclosed herein are compositions that include antigen-encoding nucleic acid sequences and/or antigen peptides. Also disclosed are nucleotides, cells, and methods associated with the compositions including their use as vaccines against infectious diseases such as HIV.