The present invention describes how a MAb specific to a viral or cancer antigen can be linked to a novel Zn porting peptide that is engineered to load ionic Zn absent requirement for biological catalysis, carry Zn stably through the circulation, release payload proximal to diseased cells, deliver its Zn cargo intracellularly due to ionophore activity, and release Zn intracellularly. As specifically designed for COVID-19, the payload can be released by furin cleavage, and the Zn released intracellularly by cleavage at a 3CL major COVID protease site replacing sequences naturally found in alpha defensin-5, as one example, or by many other variations encompassing this design. The peptide's entry and intracellular Zn release can be further facilitated by the insertion of an arginine-lysine rich membrane translocation sequence at its amino or carboxyl terminus. The design provides a novel unifying strategy for preventing and treating COVID-19 (SARS-CoV-2) infection, other coronaviral infections, influenza infections, and many cancers.

Antibodies that bind SARS-CoV spike protein, SARS-CoV-2 spike protein, and methods of using same for treating or preventing conditions associated with SARS or COVID-19 and for detecting SARS-CoV or SARS-CoV-2.

A Dengue virus Envelope Dimer Epitope (EDE) wherein the EDE: c) spans the polypeptides of a Dengue virus Envelope polypeptide dimer; and/or d) is presented on a dimer of Envelope proteins; and/or c) is formed from consecutive or non-consecutive residues of the envelope polypeptide dimer, wherein the dimer is a homodimer or heterodimer of native and/or mutant envelope polypeptides, from any one or two of DENV-1, DENV-2, DENV-3 and DENV-4. The EDE may be a stabilized recombinant dengue virus envelope glycoprotein E ectodomain (sE) dimer, wherein the dimer is: covalently stabilized with at least one disulphide inter-chain bond between the two sE monomers, and/or covalently stabilized with at least one sulfhydryl-reactive crosslinker between the two sE monomers, and/or covalently stabilized by linking the two sE monomers through modified sugars; and/or, covalently stabilised by being formed as a single polypeptide chain, optionally with a linker region, optionally a Glycine Serine rich linker region, separating the sE sequences, and/or non-covalently stabilized by substituting at least one amino acid residue in the amino acid sequence of at least one sE monomer with at least one bulky side chain amino acid, at the dimer interface or in domain 1 (D1)/domain 3 (D3) linker of each monomer. A compound, for example an antibody or antibody fragment that can neutralise more than one Dengue virus serotype, for example an antibody that can bind to an EDE of the invention.

Antibodies that bind SARS-CoV spike protein, SARS-CoV-2 spike protein, and methods of using same for treating or preventing conditions associated with SARS or COVID-19 and for detecting SARS-CoV or SARS-CoV-2.

Provided are a novel bispecific binding molecule and use thereof. The novel bispecific binding molecule-drug conjugate includes: a) a bispecific binding molecule consisting of a first binding moiety binds a tumor cell surface antigen (T) and a second antigen binding moiety binds to an internalizing effector protein (E), and b) a cytotoxic ingredient covalently conjugated to the bispecific binding molecule. The bispecific binding molecule may specifically exert cytotoxic activity against tumor cells by specifically targeting to the tumor cells through the first antigen binding moiety, and internalizing the cytotoxic ingredient into the tumor cells by the second antigen binding moiety of the bispecific binding molecule.

The present invention provides structural determinants important for binding to the stem domain of the HA protein of influenza virus, and methods of use thereof for production of high affinity neutralizing influenza virus antibodies based upon these determinants. The present invention further provides tools for determining the efficacy of an influenza virus vaccine. The present invention further provides a molecular signature useful for determining the efficacy of an influenza virus vaccine in a subject, or for predicting prior immunologic exposure or antigen responsiveness to vaccine or influenza virus infection.

A Dengue virus Envelope Dimer Epitope (EDE) wherein the EDE: c) spans the polypeptides of a Dengue virus Envelope polypeptide dimer; and/or d) is presented on a dimer of Envelope proteins; and/or c) is formed from consecutive or nonconsecutive residues of the envelope polypeptide dimer, wherein the dimer is a homodimer or heterodimer of native and/or mutant envelope polypeptides, from any one or two of DENV-1, DENV-2, DENV-3 and DENV-4. The EDE may be a stabilized recombinant dengue virus envelope glycoprotein E ectodomain (sE) dimer, wherein the dimer is: covalently stabilized with at least one disulphide inter-chain bond between the two sE monomers, and/or covalently stabilized with at least one sulfhydryl-reactive crosslinker between the two sE monomers, and/or covalently stabilized by linking the two sE monomers through modified sugars; and/or, covalently stabilised by being formed as a single polypeptide chain, optionally with a linker region, optionally a Glycine Serine rich linker region, separating the sE sequences, and/or non-covalently stabilized by substituting at least one amino acid residue in the amino acid sequence of at least one sE monomer with at least one bulky side chain amino acid, at the dimer interface or in domain 1 (D1)/domain 3 (D3) linker of each monomer. A compound, for example an antibody or antibody fragment that can neutralise more than one Dengue virus serotype, for example an antibody that can bind to an EDE of the invention.

This disclosure provides a method for preventing, treating, or managing an ebolavirus infection in a subject, where the method includes administering to a subject in need thereof an effective amount of at least one pan-ebolavirus internal fusion loop antibody or antigen-binding fragment thereof, wherein the binding domain specifically binds to the epitope on two or more ebolavirus species or strains.

The invention features immunogenic compositions and vaccines containing an optimized human immunodeficiency virus (HIV) envelope (Env) polypeptide (e.g., a stabilized trimer of optimized HIV Env polypeptides) or a polynucleotide encoding an optimized HIV Env polypeptide and uses thereof. The invention also features methods of treating and/or preventing a HIV infection by administering an immunogenic composition or vaccine of the invention to a subject (e.g., a human).

In one aspect, provided herein are antibodies that bind to Zika virus non-structural protein 1 (NS1) and compositions comprising the same. In a specific embodiment, such antibodies or compositions thereof may be used to passively immunize a subject against Zika virus. In another embodiment, such antibodies or compositions thereof may be used to diagnose a Zika virus infection. In another aspect, provided herein are recombinant NS 1 polypeptides and compositions comprising the same that may be used to immunize a subject against Zika virus disease.