Provided in this disclosure are formulations and methods including antimicrobial peptides and at least one antibiotic that can treat or prevent microbial films when applied on an object. Also provided in this disclosure are formulations and methods including antimicrobial peptides and at least one antibiotic that can treat or prevent microbial films when administered to a subject. Also provided in this disclosure are formulations and methods including administering antimicrobial peptides and at least one antibiotic that can improve the survivability of subjects with bacterial infections. Also provided in this disclosure are formulations and methods including administering antimicrobial peptides and at least one antibiotic that can improve the survivability of subjects with periprosthetic joint infection.

The present invention describes unique means for reducing autoreactivity that sensitizes against sustained treatments, and toxicity associated with administration of biologicals, in order to develop safer cancer immunotherapeutics. Short functional sequences are identified in the biologic and matched to their most homologous human counterpart. The human homologs are swapped in to replace their foreign counterparts. Alternatively, variants are selected that have exhibit less toxicity in human or primate experiments from nature, and these sequences are swapped in to replace their counterparts in the biologic. Also, human sequences that mediate the same function as foreign sequences in the biologic, but lack any sequence homology, can be swapped in for their foreign sequence counterparts. These inventions are applied to derivatize the HIV/SIV Tat protein into humanized trimers (CATS) useful for the treatment of cancer.

The present invention relates to a new vaccine delivery system. In particular, the present invention includes compositions and methods of integrally transformed non-pathogenic, commensal bacteria that can express a nucleic acid molecule of a foreign polypeptide, wherein the nucleic acid molecule that encodes the foreign polypeptide is stably integrated into genomic DNA of the bacteria. The foreign polypeptide includes a vaccine antigen that elicits an immunogenic response, an inhibitor of a pathogen, or an immune booster or modulator.

The present invention relates to a new vaccine delivery system. In particular, the present invention includes compositions and methods of integrally transformed non-pathogenic, commensal bacteria that can express a nucleic acid molecule of a foreign polypeptide, wherein the nucleic acid molecule that encodes the foreign polypeptide is stably integrated into genomic DNA of the bacteria. The foreign polypeptide includes a vaccine antigen that elicits an immunogenic response, an inhibitor of a pathogen, or an immune booster or modulator.

The present invention relates to isolated VHHs directed against human Glycophorin A. The present invention also relates to fusion proteins comprising the VHH according to the invention that is fused to at least one heterologous polypeptide and immunoconjugates comprising the VHH according to the invention that is conjugated to at least one chemical compound and their use in therapeutic or diagnostic methods.

The present invention describes a unique method of treating cancer with the administration of an improved DAGRS construct which functions as a humanized agent specifically targeting cancer cells in vivo. A specific DAGRS is described constructed of a humanized drug delivery biologic, carboxyl to an Apoptin fragment consisting of Apoptin's proline-rich SH3-binding fragment, a spacer, and a MAP kinase (MAPK) phosphorylation site, in replacement of the SH3-binding domain at HIV-1 TAT's amino terminus. Apoptin is a viral protein with incumbent immunogenicity and toxicity in humans. Improved DAGRS constructs are described that replace the viral VP3 peptide with human AKT peptide or derivative, all equivalently spaced 11 amino acids from the initial proline to the beginning of the MAPK phosphorylation site, through which technology the DAGRS is fully humanized. DAGRS provide for improved bioavailability, enhanced specific activity, and low toxicity for in vivo treatment of cancer. DAGRS are a superior method for targeting any oncogene with an inhibitory peptide.

An algorithm for humanization is described through which human functional equivalent(s) to viral product(s) are identified by alignment of peptides anchored at each end by matching functional motifs that are spaced equivalently distant in the two aligned peptides. The algorithm totally disregards the primary amino acid composition of the spacer, and as such separates from current computer algorithms that prioritize primary amino acid alignments. Accounting for spacing dictates that functional domains be oriented correctly in three dimensions. The invention taught here can be developed into computer algorithms for rapidly identifying these anchored alignments, and thereafter developing safe humanized drugs from disruptive viral activities. Computers once taught the basic rules for anchoring equivalents, can improve on the basic algorithm through artificial intelligence to expand drug development.

This disclosure relates to the genetic modification of DNMT3A gene in immune cells. In certain embodiments, the modified immune cells may be used in adoptive T cells therapies to enhance immune responses against cancer or chronic infections. In certain embodiments, the disclosure relates to deleting, changing, or inserting nucleotides within the DNMT3A gene in immune cells, e.g., human CD8 T cells, such that the DNMT3A gene product does not function for methylation. In certain embodiments, modification of the DNMT3A gene provides an improvement in antigen-specific T cells functions and/or an enhancement of the longevity of the cells.

A method of reducing a latent HIV-specific memory-CD4+ T cell pool in a subject includes the steps of: preparing at least one HIV-1 protein coding sequence from a sample obtained from the subject, wherein the sample includes HIV-1 RNA; introducing the at least one HIV-1 protein coding sequence into at least one expression construct using yeast homologous recombination; transfecting a cell with the at least one expression construct, wherein the HIV-1 protein is secreted by the cell and administering a therapeutically effective amount of the secreted HIV-1 protein and a pharmaceutically acceptable carrier to the subject, wherein the secreted HIV-1 protein stimulates latent HIV-specific memory-CD4+ T cells to induce latent HIV-1 replication resulting in HIV-specific memory-CD4+ T cell death in the subject.

The present invention relates to a viral vector for silencing a gene specifically in astrocytes comprising: an astrocyte-specific viral envelope protein, a first nucleic acid sequence encoding a transcription activator and at least one target sequence of a neuron-specific miR under the control of an astrocyte-specific promoter, anda second nucleic acid sequence encoding a RNA for silencing the gene under the control of a promoter inducible by the transcription activator.

A method of reducing a latent HIV-specific memory-CD4+ T cell pool in a subject includes the steps of: preparing at least one HIV-1 protein coding sequence from a sample obtained from the subject, wherein the sample includes HIV-1 RNA; introducing the at least one HIV-1 protein coding sequence into at least one expression construct using yeast homologous recombination; transfecting a cell with the at least one expression construct, wherein the HIV-1 protein is secreted by the cell and administering a therapeutically effective amount of the secreted HIV-1 protein and a pharmaceutically acceptable carrier to the subject, wherein the secreted HIV-1 protein stimulates latent HIV-specific memory-CD4+ T cells to induce latent HIV-1 replication resulting in HIV-specific memory-CD4+ T cell death in the subject.