Compositions and methods of the present invention relating to B. burgdorferi HtrA sensu lato (BbHtrA) protease activity, its substrates, cleavage products, biological effects and use in detection, diagnosis and/or treatment of Lyme disease are provided.

Alpha-glycosylceramide compounds capable of activating NKT cells and compositions thereof are disclosed. Methods for activating NKT cells, methods of stimulating an immune response in a subject, and methods of treating cancer, infectious diseases, autoimmune diseases and disorders, or allergy diseases or disorders with the compounds and compositions are also disclosed.

The present disclosure provides an antibody or an antigen-binding fragment thereof with binding specificity for human interleukin-1 receptor accessory protein (IL1 RAP) wherein the antibody or antigen-binding fragment is capable of inhibiting the binding of antibody CAN04 to human IL1 RAP. The disclosure further provides the use of such antibodies or an antigen-binding fragments in the treatment and/or diagnosis of IL-1 associated diseases and conditions, including cancers such as acute myeloid leukemia and melanoma.

The present invention includes a method of delivering a therapeutic agent into and across an endothelial cell (EC) in a subject in need thereof, comprising: attaching to a T Cell receptor mimic (TCR mimic) an active agent to form a therapeutic agent; and administering to the subject the therapeutic agent in a pharmaceutically acceptable carrier, wherein the therapeutic agent effectively crosses the EC microvascular barrier. Furthermore, the present invention relates to methods of treating diseases (particularly neuronal diseases) or conditions comprising identifying a subject in need of such a treatment and administering to said subject a composition comprising a TCR mimic conjugated to an active agent.

Described herein is the generation of optimized H5N1 and H1N1 influenza HA polypeptides for eliciting a broadly reactive immune response to influenza virus isolates. The optimized HA polypeptides were developed through a series of HA protein alignments, and subsequent generation of consensus sequences, based on H5N1 and H1N1 influenza isolates. Provided herein are optimized H5N1 and H1N1 influenza HA polypeptides, and compositions, fusion proteins and VLPs comprising the HA polypeptides. Further provided are codon-optimized nucleic acid sequences encoding the HA polypeptides. Methods of eliciting an immune response against influenza virus in a subject are also provided by the present disclosure.

Provided herein are methods and reagents for treating cancer. Methods of treating cancer are provided, comprising administering to a patient in need thereof an effective amount of a DKK1 peptide-loaded MHC antibody provided herein. The methods can further include administering an effective amount of chemotherapy or immunotherapy to said patient.

ProTGF1-GARP complex-selective antibodies, polynucleotides capable of encoding the proTGF1-GARP complex-selective antibodies or antigen-binding fragments, cells expressing proTGF1-GARP complex-selective antibodies or antigen-binding fragments, as well as associated vectors and detectably labeled proTGF1-GARP complex-selective antibodies or antigen-binding fragments may be used to enhance an immune response in a subject, for example, against a cancer.

Antigen binding proteins that bind to human CGRP receptor (CGRP R) are provided. Nucleic acids encoding the antigen binding protein, vectors, and cells encoding the same are also provided. The antigen binding proteins can inhibit binding of CGRP R to CGRP, and are useful in a number of CGRP R related disorders, including the treatment and/or prevention of migraine headaches.

The present invention provides compositions and methods relating to or derived from antigen binding proteins activate FGF21-mediated signaling. In embodiments, the antigen binding proteins specifically bind to (i) -Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising -Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. In some embodiments the antigen binding proteins induce FGF21-like signaling. In some embodiments, an antigen binding protein is a fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to (i) -Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising -Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. Other embodiments provide nucleic acids encoding such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins, fragments and derivatives thereof, and polypeptides, including methods of treating or diagnosing subjects suffering from type 2 diabetes, obesity, NASH, metabolic syndrome and related disorders or conditions.

This invention provides monoclonal antibodies that recognize the Toll-like Receptor 4/MD-2 receptor complex, and monoclonal antibodies that recognize the TLR4/MD2 complex as well as TLR4 when not complexed with MD-2. The invention further provides methods of using the monoclonal antibodies as therapeutics. This invention also provides soluble chimeric proteins, methods of expressing and purifying soluble chimeric proteins, and methods of using soluble chimeric proteins as therapeutics, in screening assays and in the production of antibodies.