The invention provides novel broadly neutralizing antibodies and related antibody compositions against betacoronaviruses, e.g., SARS-CoV-2. Also provided in the invention are polynucleotides and vectors encoding such antibodies, as well as pharmaceutical compositions containing the antibodies or polynucleotides. Therapeutic uses of the antibodies or pharmaceutical compositions in preventing or treating betacoronaviral infections (e.g., SARS-CoV-2 infection) are also encompassed by the invention.

Provided herein are monoclonal antibodies that specifically bind to an anti-SARS-CoV-2 spike(S) protein, and methods of using said antibodies.

Provided are innovative compositions for tethering blocking an inactivating of airborne respiratory infectious viruses. The compositions comprise bispecific proteins with two different antigen binding regions (ABR), which are typically configured as immunoglobulin single variable domains (ISV). A first ISV binds to a surface protein found on an airborne infectious virus. A second ISV binds to a mucin protein, e.g. a mucin protein present on ocular, nasopharyngeal, tracheal and/or oral surfaces of a mammal. The two ISV are joined by a polypeptide linker.

Provided are innovative compositions for tethering blocking an inactivating of airborne respiratory infectious viruses. The compositions comprise bispecific proteins with two different antigen binding regions (ABR), which are typically configured as immunoglobulin single variable domains (ISV). A first ISV binds to a surface protein found on an airborne infectious virus. A second ISV binds to a mucin protein, e.g. a mucin protein present on ocular, nasopharyngeal, tracheal and/or oral surfaces of a mammal. The two ISV are joined by a polypeptide linker.

Provided are methods for treating cancer using local administration of certain CpG oligonucleotides (CpG ODN) and systemic administration of a checkpoint inhibitor such as an anti-PD-1 antibody, an anti-PD-L1 antibody, and/or an anti-CTLA-4 antibody. In preferred embodiments, the CpG ODN are selected based on their propensity to induce high amounts of interferon alpha (IFN-) and T-cell activation relative to interleukin-10 (IL-10) and B-cell activation. In certain embodiments, the methods further include pretreatment with radiotherapy, to potentiate the combination immunotherapy.

The present disclosure provides antibodies and antigen-binding fragments thereof that bind specifically to a coronavirus spike protein and methods of using such antibodies and fragments for treating or preventing viral infections (e.g., coronavirus infections).

Provided herein are methods for preparing and characterizing SARS-cov2 antigen specific immune cell cultures and preparations and methods of using the same in adoptive immunotherapy for cancer, infections, and immune disorders. Also provided are compositions and methods for generating immune calls expressing synthetic antigen binding receptors targeting SARS-cov2 and methods of use of these cells for the treatment and prevention of COVID-19. Also provided are compositions and methods for determining immune response to SARS-cov2 in a subject, detecting SARS-cov2, measuring cytotoxicity induced by SARS-cov2, and detecting the expression and cytotoxicity of synthetic antigen binding receptors targeting SARS-cov2.

Among the various aspects of the present disclosure is the provision of compositions and methods of use of mAb that prevent, inhibit, or reduce the transmissivity of SARS-CoV-2 infections.

Disclosed are assays, reagents, and methods for ultrasensitive detection of target molecules. The assay comprises fusion proteins including binding moieties, such as antibodies, nanobodies (VHH/VNAR), or aptamers, linked to nonfunctional fragments of a protein. In the presence of a target molecule, the binding moieties recognize distinct target regions and bring the protein fragments into close proximity, reconstituting a functional protein that generates a detectable signal. Linkers connecting the fusion components may be flexible peptides or polypeptides that spontaneously form dimers, trimers, or tetramers, thereby providing multivalent fusion proteins with enhanced sensitivity. The reconstituted protein may produce luminescent, fluorescent, colorimetric, or spectroscopic signals detectable by microplate readers, handheld luminometers, or lateral flow devices. The invention encompasses solid-phase, homogeneous, and lateral flow assay formats for detecting viruses, bacteria, proteins, peptides, or small molecules, including GLRaV-3, SARS-CoV-2, PSA, and E. coli. The disclosed assays exhibit improved specificity, reduced background, and enhanced signal-to-noise ratios.

The present disclosure is directed to antibodies and antigen binding fragments thereof, or combinations of antibodies and antigen binding fragments thereof, having binding specificity for the S protein of coronaviruses (CoV-S), such as the S protein of the SARS coronavirus 2 (SARS-CoV-2-S), including neutralizing antibodies. The antibodies and antigen binding fragments thereof comprise the sequences of the VH, VL, and CDR polypeptides described herein, and the polynucleotides encoding them. The disclosure contemplates conjugates of anti-CoV-S antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. Methods of making said anti-CoV-S antibodies and antigen binding fragments thereof are also contemplated. Other embodiments of the disclosure contemplate using anti-CoV-S antibodies, and binding fragments thereof, for the diagnosis, assessment, and treatment of diseases and disorders associated with coronaviruses or the S protein thereof and conditions where neutralization or inhibition of coronaviruses or the S protein thereof would be therapeutically beneficial.