The present invention provides methods, immunoglobulin compositions and vector constructs as a general approach to provide episomal based immune protection from the 2019 novel coronavirus (COVID-19), its variants/mutants and other pandemic and even non-pandemic viruses. The immunoglobulin compositions include the heavy chain variable, diversity and joining (VDJ or Variable Heavy Region genes) segment immunoglobulin DNA and/or polypeptide sequence from humans identified to have developed high affinity immunoglobulins (ideally antibodies with nanomolar to picomolar dissociation constants to virus proteins with additional emphasis on cell surface proteins and further emphasis on the Spike protein as related to COVID-19) against the virus of interest and either to use the exact immunoglobulin composition identified from the donor or to combine that variable immunoglobulin region for both heavy and light chains with a non-divergent well-conserved amino acid sequence for the constant regions especially, Hinge region, Constant Heavy 2 (C.sub.H2) and Constant Heavy 3 (C.sub.H3) for the immunoglobulin heavy chain polypeptide with optional use of donor based Constant Heavy 1 (C.sub.H1) or non-divergent well conserved C.sub.H1 heavy chain constant region and optional use of hinge region peptides. The immunoglobulin light chain will use either entirely donor based amino acid sequence or donor based light chain variable and joining (VJ or Variable light region genes) segments immunoglobulin polypeptide sequence with a well-conserved non-divergent constant light (C.sub.L) chain region for immunoglobulin Kappa locus (κ) or immunoglobulin lambda locus (λ) light chain. The resulting antibodies can either be used as a monoclonal or polyclonal mix of (Immunoglobulin Class G subclass1) IgG1, IgG3 and other subclasses, IgA1 monomer and IgA2 monomer and dimeric IgA1 (dIgA1) immunoglobulins (as identified by the potency of associated memory B-cells) to be expressed via intramuscular administration, intravenous or proximal to lymph nodes. The immunoglobulins will be expressed in the vaccine/immunization recipient via an episome. The vector will be ideally delivered in a recombinant Adeno Associated Virus (rAAV) with preference for AAV serotype 8 (AAV8) containing a single-stranded Deoxyribonucleic acid (ssDNA) non-viral vector or lentivirus virion containing double stranded DNA as a non-viral vector. A single non-viral vector will code for the entire immunoglobulin and J-chain expression for dIgA1 where expression will occur with a single start codon and stop codon for the amino acid sequence and in some embodiments a second start codon for J chain expression. The specific DNA

The present invention is directed to recombinant lentiviral particles that array the SARS-CoV-2 spike (S) protein on their surface (“SARS-CoV-2 S Protein Lentiviral Particles”), and that optionally comprise an additional copy of a polynucleotide encoding the SARS-CoV-2 spike (S) protein in their viral genome, and to methods for the production of such lentiviral particles. The invention particularly pertains to such SARS-CoV-2 S Protein Lentiviral Particles that have been engineered to be incapable of mediating the integration of their lentiviral genome into the chromosomes of infected cells and/or to be incapable of mediating the reverse transcription of their lentiviral genome. The present invention is also directed to “SARS-CoV-2 S Protein Lentiviral Vaccine” pharmaceutical compositions that comprise such SARS-CoV-2 S Protein Lentiviral Particles. The present invention is additionally directed to the use of such SARS-CoV-2 S Protein Lentiviral Vaccine pharmaceutical compositions for providing immunity to COVID-19 infection to humans and other mammals, either directly or as an inactivated form.

The disclosure relates generally to nucleic acid vectors and packaging cell lines for in vivo expansion of T-cells. More particularly, the disclosure relates to direct intratumoral injection of a lentiviral vector adapted for transduction and drug-mediated expansion of tumor-infiltrating lymphocytes in vivo.

An enveloped viral particle producer or packaging cell, wherein the cell is genetically engineered to decrease expression of MHC-I on the surface of the cell.

The present invention provides for novel compositions and methods for delivering genes of interest to stem cells using vectors that contain differentiation-specific transcriptional regulatory elements. For example, stem cells in the internal epithelia could be transfected with a vaccine construct, which has an epithelial cell differentiation-specific promoter driving the expression of viral envelope proteins. When the promoter used is specific for terminally differentiated epithelial cells, then the viral envelope proteins will be expressed only in the upper part of the epithelia and therefore, stimulate the immune response. The infected epithelial stem cells in the basal layer will continue to produce new antigen-expressing cells, without being eliminated by the immune response. This invention will be useful in the development of vaccines against viral agents that target the internal mucosa like HIV.

Hematopoietic stem/progenitor cells (HSPC) and/or non-T effector cells are genetically modified to express (i) an extracellular component including a ligand binding domain that binds a cellular marker preferentially expressed on an unwanted cell; and (ii) an intracellular component comprising an effector domain. Among other uses, the modified cells can be administered to patients to target unwanted cancer cells without the need for immunological matching before administration.

The present invention relates generally to immunization and immunotherapy for the treatment or prevention of HIV. In particular, the methods relate to in vivo and ex vivo enrichment of HIV-specific CD4 T cells. In certain embodiments, the disclosed compositions and methods can incorporate therapy in order to further enhance the HIV-specific CD4 T cells.

Hematopoietic stem/progenitor cells (HSPC) and/or non-T effector cells are genetically modified to express (i) an extracellular component including a ligand binding domain that binds a cellular marker preferentially expressed on an unwanted cell; and (ii) an intracellular component comprising an effector domain. Among other uses, the modified cells can be administered to patients to target unwanted cancer cells without the need for immunological matching before administration.

An enveloped viral particle producer or packaging cell, wherein the cell is genetically engineered to decrease expression of MHC-I on the surface of the cell.

The invention provides improved gene therapy methods and compositions.