Provided herein are compounds having the structure of Formulas A-D and compositions thereof for use in the detection and quantification of viral neuraminidase. In particular, the compounds may be useful for the evaluation of viral strains and for vaccine evaluation.

The present application provides methods and compositions for treating cancers (such as solid tumors) using a recombinant oncolytic virus encoding a sialidase. In some embodiments, the oncolytic virus further encodes one or more other heterologous proteins. In some embodiments, the recombinant oncolytic virus is delivered via an engineered immune cell. In some embodiments, the present application provides methods and compositions for treating cancers using a recombinant oncolytic vims encoding a sialidase or another heterologous protein and an engineered immune cell (e.g., a CAR-T, CAR-NK, or CAR-NKT cell) expressing a chimeric receptor capable of binding to the sialidase or other heterologous protein.

Recombinant constructs, influenza viral genomes including the recombinant constructs, influenza viruses including the constructs, and vaccine formulations formed thereof for inducing or increasing an immune response against influenza virus are provided. The compositions typically include a nucleic acid having a nucleic acid sequence encoding IgA-inducing protein (IGIP) polypeptide that can positively regulate IgA expression operably linked to expression of a hemagglutinin or a neuraminidase. When the nucleic acid is expressed by recombinant influenza virus in infected cells, it preferably enhances IgA production against influenza virus. Live attenuated virus expressing IGIP, and methods of use thereof for treating and preventing influenza infections are also provided.

Provided are conjugates including a targeting moiety that binds to a cell surface molecule of a target cell and a target cell surface-editing enzyme. Also provided are compositions and kits that include the conjugates, as well as methods of using the conjugates. Methods of making conjugates are also provided.

The present invention provides, among other things, a novel and improved method for generating “mosaic” influenza antigenic polypeptides including hemagglutinin (HA) and neuraminidase (NA) polypeptides based on unique combination of epitope patterns that maximize exposure to epitopes present across multiple HA or NA sequences and therefore improved influenza strain coverage. In particular, the present invention provides engineered H1N1 influenza hemagglutinin (HA) polypeptides that are comprised of novel combinations of protective epitopes and antigenic regions from multiple H1N1 viral strains. Such engineered HA polypeptides have improved properties over HA polypeptides developed through conventional approaches that rely on consensus alignments of viral sequences.

The present disclosure provides novel adjuvants which may be used in combination with one or more antigens to augment, modulate or enhance a host immune response to the one or more antigens. The adjuvants are based on sialic acid binding molecules and may be combined with any type of antigen. The adjuvants may be formulated for mucosal and/or intranasal administration.

The present disclosure relates to methods of targeting specific cell types within the retina using optimized gene therapy vectors in combination with a glycoside hydrolase enzyme, such as neuraminidase. In particular, the disclosure provides gene therapy vectors administered with a glycoside hydrolase enzyme to specifically target retinal cells and methods of treating visual impairment, retinal degeneration and vision-related disorders.

The present invention relates to a nucleic acid vaccine. Specifically, the use of a single nucleic acid sequence comprising combinations of influenza genes coding for selected hemagglutinin (HA), neuraminidase (NA), matrix protein 1 (M1), matrix protein 2 (M2) and nucleoprotein (NP) interspaced with selected linkers comprising cleavage sites to produce individual proteins, together forming one polyvalent influenza vaccine for use in medicine for humans and animals.

In one aspect, provided herein are mutated influenza virus neuraminidase polypeptides, wherein the mutated influenza virus neuraminidase polypeptides comprise a first cytoplasmic domain, a first transmembrane domain, a first stalk domain, and a first globular head domain of a first neuraminidase of a first influenza virus with an insertion of 15 to 45 or 1 to 50 amino acid residues in the first stalk domain of the first neuraminidase. In another aspect, provided herein is an influenza virus comprising such a mutated influenza virus neuraminidase polypeptide, a genome comprising a nucleotide sequence encoding such a mutated influenza virus neuraminidase polypeptide or both. In another aspect, provided herein is an immunogenic composition comprising such an influenza virus, and optionally an adjuvant.

This disclosure relates to glycoengineering, and methods of utilizing glycoengineering for treating various diseases or disorders (e.g., IgE-mediated disorders). The methods include administering to the subject an effective amount of a composition comprising a fusion protein described herein. In some embodiments, the IgE-mediated disorder is an allergic disorder. In some embodiments, the allergic disorder is an anaphylactic allergy.