Abstract: Antibodies and antigen binding fragments that specifically bind to P. falciparum circumsporozoite protein are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. The disclosed antibodies, antigen binding fragments, nucleic acids and vectors can be used, for example, to inhibit a P. falciparum infection.

Abstract: Embodiments herein report compositions, uses and manufacturing of dengue virus constructs and live attenuated dengue viruses. Some embodiments concern a composition that includes, but is not limited to, a tetravalent dengue virus composition. In certain embodiments, compositions can include constructs of one or more serotypes of dengue virus, such as dengue-1 (DEN-1) virus, dengue-2 (DEN-2) virus, dengue-3 (DEN-3) or dengue-4 (DEN-4) virus constructs. In other embodiments, constructs disclosed herein can be combined in a composition to generate a vaccine against more one or more dengue virus constructs that may or may not be subsequently passaged in mammalian cells.

Abstract: Disclosed herein are modified NK cells, compositions comprising modified NK cells, and methods for treating a tumor or hyperproliferative disease in a subject. In some embodiments, the modified NK cells include NK cells including a heterologous nucleic acid molecule encoding a CD16 protein comprising a valine at amino acid position 158 (CD16-V158), a heterologous nucleic acid molecule encoding a CCR7 protein, or both. In some embodiments, methods include treating a subject with a tumor by administering a composition comprising an anti-cancer monoclonal antibody and administering a composition comprising the modified NK cells to the subject. Also disclosed are methods of making modified NK cells by obtaining a population of NK cells from a subject and transfecting the population of NK cells with a heterologous nucleic acid molecule encoding CD16-V158, a heterologous nucleic acid molecule encoding a CCR7 protein, or both.

Abstract: Provided herein are nucleic acid molecules encoding a SARS-CoV-2 S ectodomain—HBsAg fusion protein. When expressed in mammalian cells (for example, by administration to a mammalian subject), the fusion protein self-assembles to form a HBsAg protein nanoparticle with SARS-CoV-2 S ectodomain trimers extending radially outward from an outer surface of the HBsAg protein nanoparticle. Thus, in several aspects, the disclosed nucleic acid molecule can be used to generate an immune response to SARS-CoV-2 in a subject.

Abstract: Embodiments of vesicles comprising embedded cytotoxic agents are disclosed, as well as methods of making and using the vesicles. Pharmaceutical compositions including the vesicles also are disclosed. The vesicles include a binary lipid bilayer surrounding a cavity, wherein the vesicle binary lipid bilayer includes (i) a non-bilayer forming lipid (or combination of non-bilayer forming lipids) and a PEGylated lipid; and (i) a cytotoxic agent embedded within the vesicle wall.

Abstract: The invention provides an isolated and purified nucleic acid sequence encoding a chimeric antigen receptor (CAR) directed against B-cell Maturation Antigen (BCMA). The invention also provides host cells, such as T-cells or natural killer (NK) cells, expressing the CAR and methods for destroying multiple myeloma cells.

Abstract: Camel single-domain monoclonal antibodies that specifically bind human and mouse mesothelin are described. Chimeric antigen receptor (CAR) T cells and antibody conjugates based on the mesothelin-specific antibodies are also described. The disclosed CAR T cells, mesothelin-specific antibodies and conjugates thereof can be used, for example, in the diagnosis or treatment of mesothelin-positive cancers.

Abstract: Embodiments of immunogens based on the outer domain of HIV-1 gp120 and methods of their use and production are disclosed. Nucleic acid molecules encoding the immunogens are also provided. In several embodiments, the immunogens can be used to prime an immune response to gp120 in a subject, for example, to treat or prevent an HIV-1 infection in the subject.

Abstract: Disclosed are methods of isolating T cells having antigenic specificity for a mutated amino acid sequence encoded by a cancer-specific mutation, the method comprising: identifying one or more genes in the nucleic acid of a cancer cell of a patient, each gene containing a cancer-specific mutation that encodes a mutated amino acid sequence; inducing autologous APCs of the patient to present the mutated amino acid sequence; co-culturing autologous T cells of the patient with the autologous APCs that present the mutated amino acid sequence; and selecting the autologous T cells. Also disclosed are related methods of preparing a population of cells, populations of cells, pharmaceutical compositions, and methods of treating or preventing cancer.

Abstract: Single-domain monoclonal antibodies (“nanobodies”) that specifically bind the S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein are described. The single-domain antibodies were isolated from shark variable domain of new antigen receptor (VNAR) and camel variant domain of heavy chain only antibody (VHH) phage display libraries panned against the S2 subunit of SARS-CoV-2 spike protein. The S2 subunit-specific nanobodies, and conjugates thereof, can be used for the diagnosis and treatment of a coronavirus infection.

Abstract: Methods are disclosed herein for modulating osteoclast fusion. In some embodiments, these methods include administering an effective amount of a Lupus autoantigen (La) protein, or an agent that modulates La protein expression or activity, to a subject in need thereof, thereby modulating osteoclast fusion in the subject. In some embodiments, the method increases osteoclast fusion and bone resorption. In other embodiments, the method decreases osteoclast fusion and bone resorption.

Abstract: The invention features modified alphavirus or flavivirus virus-like particles (VLPs). The invention provides methods, compositions, and kits featuring the modified VLPs. The invention also features methods for enhancing production of modified VLPs for use in the prevention or treatment of alphavirus and flavivirus-mediated diseases. The invention also provides methods for delivering agents to a cell using the modified VLPs.

Abstract: Disclosed herein are methods of diagnosing, and treating and/or preventing CD55-deficiency, hyperactivation of complement, angiopathic thrombosis and protein-losing enteropathy (CHAPLE). The method of diagnosing includes: providing a sample from a patient; performing an assay detecting at least one of at least one mutation in a DNA sequence of a CD55 gene, at least one mutation in a RNA sequence of a CD55 transcript, at least one mutation in a DNA sequence of a CD55 complementary-DNA (cDNA), CD55 protein, CD55 protein binding, complement deposition or combination thereof, and diagnosing the patient with CHAPLE. The method of treating and/or preventing at least one symptom of CHAPLE includes: administering an effective amount of a composition comprising at least one complement inhibitor to a subject in need thereof, wherein the composition is effective in treating or preventing at least on symptom of CHAPLE. The disclosure further relates to compositions effective at treating and/or preventing CHAPLE.

Abstract: The present invention provides a method of treating a subject afflicted with cancer comprising administering to the subject an effective amount of a PP2A inhibitor.

Abstract: The present disclosure provides compositions for viral gene therapy, e.g. Adeno-Associated virus-directed gene therapy, and methods of using the same for the treatment and/or prevention of cholesterol storage diseases or disorders, such as Niemann-Pick disease, Type C.

Abstract: Disclosed herein are novel methods of treating substance use disorders, mitigating the development of substance addiction, reducing the severity of substance withdrawal symptoms, or reducing or preventing substance relapse by providing to the patient a therapeutically effective amount of a Medication Assisted Treatment agent and a selective dopamine D3 receptor antagonist/partial agonist. In addition, the D3 antagonists/partial agonists described herein may be used to augment the effectiveness of current Medication Assisted Treatment regimens (e.g. methadone or buprenorphine) for the treatment of substance use disorders, including opioid use disorders.

Abstract: Disclosed herein novel dopamine D3 receptor selective antagonists/partial agonists compounds with high affinity and metabolic stability useful for the treatment of psychiatric and neurological disorders and as research and diagnostic tools. Also disclosed are methods of making the compounds.

Abstract: A compound of Formula I or a pharmaceutically acceptable ester, amide, solvate, or salt thereof, or a salt of such an ester or amide or a solvate of such an ester amide or salt: wherein the definitions of R1-R13 and L1-L4 are provided in the disclosure, and wherein R14 is a group capable of binding to prostate-specific membrane antigen (PSMA).

Abstract: Embodiments of recombinant HIV-1 gp120 proteins that contain a V1 deletion are disclosed. Also provided are gp140, gp145, and gp160 proteins containing the V1 deletion, as well as HIV-1 Env ectodomain trimers containing protomers containing the V1 deletion. Nucleic acid molecules encoding these proteins are also provided. In several embodiments, the disclosed recombinant HIV-1 proteins and/or nucleic acid molecules can be used to generate an immune response to HIV-1 in a subject, for example, to treat or prevent an HIV-1 infection in the subject.

Abstract: Methods for producing synthetic single-domain monoclonal antibody libraries using humanized llama nanobody framework sequences, libraries obtainable by the method, as well as antibodies selected from the libraries are described. In particular, synthetic single-domain monoclonal antibodies that specifically bind to the spike protein of SARS-COV-2 and neutralize SARS-COV-2 infection are described. Use of the disclosed antibodies for the detection, prophylaxis and treatment of SARS-COV-2 infection is described.