Provided herein are compositions and methods for treating autoimmune diabetes such as type 1 diabetes (T1D), diagnosing autoimmune diabetes such as T1D, assessing treatment efficacy, and selecting subjects for treatment, e.g., using a peptide or epitope disclosed.

A novel IFN-/ independent ligand receptor system which upon engagement leads, among other things, to the establishment of an anti-viral state is disclosed. Further disclosed are three closely positioned genes on human chromosome 19 that encode distinct but highly homologous proteins, designated IFN-1, IFN-2, IFN-3, based inter alia, in their ability to induce antiviral protection. Expression of these proteins is induced upon viral infection. A receptor complex utilized by all three IFN- proteins for signaling is also disclosed. The receptor complex is generally composed of two subunits, a novel receptor designated IFN-R1 or CRF2-12, and a second subunit, IL-10R2 or CRF2-4, which is also a shared receptor component for the IL-10 and IL-22 receptor complexes. The gene encoding IFN-R1 is generally widely expressed, including many different cell types and tissues. Expression of these proteins is induced by immune events, including, for example, upon viral infection. Apoptotosis may also be induced under effective conditions.

Antibiotics (Abx) are the worlds most misused drugs. Antibiotics misuse occurs when the drug is administered in case of a non-bacterial infection (such as a viral infection) for which it is ineffective. Overall, it is estimated that 40-70% of the worldwide Abx courses are mis-prescribed. The financial and health consequences of Abx over-prescription include the direct cost of the drugs, as well as the indirect costs of their side effects, which are estimated at >$15 billion annually. Furthermore, over-prescription directly causes the emergence of Abx-resistant strains of bacteria, which are recognized as one of the major threats to public health today. This generates an immediate need for reliable diagnostics to assist physicians in correct Abx prescription, especially at the point-of-care (POC) where most Abx are prescribed. Accordingly, some aspects of the present invention provide methods using biomarkers for rapidly detecting the source of infection and administrating the appropriate treatment.

Compositions and methods are provided for detection, diagnosis and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) and for characterization of SARS-CoV-2 antigen-specific T-cell immune responsiveness in COVID-19 patient samples, including in secondary in vitro immune response assays for long-lived anamnestic (memory) T-cell responses. Disclosed compositions and methods include a method that comprises contacting, in vitro, whole blood samples from subjects suspected of having COVID-19 or who have previously been exposed to SARS-CoV-2, with synthetic peptides comprising T-cell epitope-containing regions derived from SARS-CoV-2 Spike proteins; and indirectly detecting SARS-CoV-2-specific activated T-cells by determining production of a T-cell immune response indicator (e.g., interferon-) in response to stimulation by the Spike protein-derived peptides.

The current invention provides methods to identify 92T-cell receptors (92TCR) that mediate anti-tumour responses. Surprisingly, it was now found that the CDR3 regions of the 9-T-cell receptor chain and the 2-T-Cell receptor chain (2TCR chain) are of importance. Based on these findings, combinatorial-TCR-chain-exchange (CTE) is proposed as an efficient method for identifying 92TCRs that mediate anti-tumour responses. Using the method of the invention, specific sequences of the respective 9TCR and 2TCR chains were identified that mediate anti-tumour responses. Hence, the invention further provides for specific 92TCRs, or fragments thereof, that may be used e.g. in diagnostics or treatment of cancer. The invention further provides for nucleic acid sequences, genetic constructs and retroviral vectors that can be used to express the 92TCRs according to the invention.

The invention provides compositions and methods of predicting a subject's risk of developing age-related macular degeneration (AMD) and methods of treating, delaying, or preventing the development and progression of AMD.

Described herein are compositions for increasing IL-12 production comprising IgG or a fragment thereof or a variant thereof and uses of said compositions for treating cancer and infectious diseases. Also described herein are compositions for decreasing IL-12 production comprising an agent that inhibits signaling mediated by interaction between FcRn and IgG and uses of said compositions for treating autoimmune diseases. Further described herein are methods for assessing efficacy of treatment by monitoring levels of various cytokines in the subject.

The invention relates to biomarkers associated with preterm delivery. More specifically, the invention provides methods of measuring biomarkers including but not limited to cytokines, cytokine receptors, cytokine receptor antagonists, chemokines, chemokine receptors, and/or chemokine receptor antagonists found in women that are at risk for preterm delivery. The diagnostic methods may be performed on whole blood.

Described herein are compositions for increasing IL-12 production comprising IgG or a fragment thereof or a variant thereof and uses of said compositions for treating cancer and infectious diseases. Also described herein are compositions for decreasing IL-12 production comprising an agent that inhibits signaling mediated by interaction between FcRn and IgG and uses of said compositions for treating autoimmune diseases. Further described herein are methods for assessing efficacy of treatment by monitoring levels of various cytokines in the subject.

The present disclosure provides for proprotein and activatable proprotein compositions. A proprotein contains a functional protein (i.e. a full length protein or functional fragment thereof) which is coupled to a peptide mask that inhibits the binding of the functional protein to its target or binding partner. An activatable proprotein contains a functional protein coupled to a peptide mask, and further coupled to an activatable linker, wherein in an non-activated state, the peptide mask inhibits binding of the functional protein to its target or binding partner and in an activated state the peptide mask does not inhibit binding of the functional protein to its target or binding partner. Proproteins can provide for reduced toxicity and adverse side effects that could otherwise result from binding of a functional protein at non-treatment sites if it were not inhibited from binding its binding partner. Proproteins can further provide improved biodistribution characteristics. Proproteins containing a peptide mask can display a longer in vivo or serum half-life than the corresponding functional protein not containing a peptide mask. The disclosure further provides methods of screening for, making, and using these proproteins.