Methods are provided for the prognosis, diagnosis and treatment of various pathological states, including cancer, chemotherapy resistance and dementia associated with Alzheimer's disease. The methods provided herein are based on the discovery that various proteins with a high level of sialylation are shown herein to be associated with disease states, such as, cancer, chemotherapy resistance and dementia associated with Alzheimer's disease. Such methods provide a lysosomal exocytosis activity profile comprising one or more values representing lysosomal exocytosis activity. Also provided herein, is the discovery that low lysosomal sialidase activity is associated with various pathological states. Thus, the methods also provide a lysosomal sialidase activity profile, comprising one or more values representing lysosomal sialidase activity. A lysosomal sialidase activity profile is one example of a lysosomal exocytosis activity profile.

In one aspect, provided herein are recombinant neuraminidases comprising an ectodomain of influenza virus neuraminidase with amino acid substitutions or insertions of cysteines in the stalk domain to generate a more stable, tetrameric influenza virus neuraminidase. In specific embodiments, the influenza virus neuraminidase further comprises influenza virus neuraminidase transmembrane and cytoplasmic domains. In another aspect, provided herein are recombinant neuraminidase comprising a globular head domain of influenza virus neuraminidase and a tetramerization domain, wherein the recombinant neuraminidase lacks influenza virus neuraminidase stalk, transmembrane and cytoplasmic domains. In another aspect, provided herein are methods of immunizing against influenza virus using such recombinant neuraminidases or compositions thereof.

The invention relates generally to recombinant sialidase and anti-HER2 immunoglobulin antigen-binding domain fusion proteins. The invention also provides antibody conjugates including a sialidase and an anti-HER2 antibody or a portion thereof. The invention further relates to methods of using the sialidase fusion proteins or antibody conjugates for treating cancer.

The invention relates generally to recombinant sialidase and anti-CD20 immunoglobulin antigen-binding domain fusion proteins. The invention also provides antibody conjugates including a sialidase and an anti-CD20 antibody or a portion thereof. The invention further relates to methods of using the sialidase fusion proteins or antibody conjugates for treating cancer.

Recombinant oncolytic viruses for expression of sialidase and their use in the treatment of cancer, particularly solid tumors, are described.

The invention relates generally to recombinant sialidase and anti-PD-L1 immunoglobulin antigen-binding domain fusion proteins. The invention also provides antibody conjugates including a sialidase and an anti-PD-L1 antibody or a portion thereof. The invention further relates to methods of using the sialidase fusion proteins or antibody conjugates for treating cancer.

The invention relates generally to recombinant sialidases, methods and compositions for extending the serum half-life of the recombinant sialidases, and use of the same in the treatment of a sialic acid-related disorder.

Provided are a modified-type neuraminidase, a gene encoding the modified-type neuraminidase, a combination of the modified-type neuraminidase and cathepsin A, a combination of the gene encoding the modified-type neuraminidase and a gene encoding cathepsin A, a vector including said genes, and a pharmaceutical composition containing same. The pharmaceutical composition can be used for the therapy of lysosomal storage disease.

The invention relates generally to recombinant human sialidases and recombinant sialidase fusion proteins, wherein the sialidase optionally contains one or more mutations compared to wild-type human sialidase, e.g., a substitution, deletion, or addition of at least one amino acid. The invention also provides antibody conjugates including a sialidase and an antibody or a portion thereof. The invention further relates to methods of using the sialidase fusion proteins or antibody conjugates for treating cancer.

The present invention relates to expression of SARS-CoV like virus proteins [S, M and E] proteins; recombinant polynucleotides, polypeptides; constructs, virus-like particles (VLPs); immunogenic compositions or vaccines comprising Virus Like Particles (VLPs). Method of producing the VLPs/expressing the multi-subunit virus like proteins and method for co-expression of multi-subunit and virus like proteins (VLPs) are also provided. The present invention also provides strategies, methods, systems, kits and combinations for scalable expression, purification and enhanced production of the virus like proteins of SARS-CoV while maintaining their size range and composition. Such multi-subunit VLPs can be utilized to make immunogenic compositions or vaccines.