Provided herein are compositions comprising VHH conjugates and their uses in treating diseases.

Contemplated compositions and methods generate a durable immune synapse and so lead to activated T-cells and memory T-cell formation by use of selected co-stimulatory receptors and their ligands in conjunction with selected neoepitopes. Moreover, immune competent cells are attracted into a tumor microenvironment after activation of the T-cells using hybrid or chimeric binding proteins that comprise a chemokine portion and that target components of necrotic cells.

The present invention concerns a method for treating triple-negative breast cancer (TNBC) in an individual, and/or for inducing an immune response to HER2/neu in an individual with a triple-negative breast cancer expressing low levels of HER2/neu, the method comprising administering to the individual: (a) an effective amount of trastuzumab, or derivative thereof; and (b) an effective amount of nelipepimut-S, or variant thereof, optionally with an immunological adjuvant. Preferably, the method includes a preparatory or priming phase comprising a frequency and duration of trastuzumab or trastuzumab derivative administration sufficient to substantially increase the major histocompatibility complex (MHC)-mediated presentation of HER2 peptide fragments to the patient immune system. The invention also includes medicaments and kits for treating TNBC in an individual, and/or for inducing an immune response to HER2/neu in an individual with a TNBC expressing HER2/neu.

A set of target peptides are presented by HLA A*0101, A*0201, A*0301, B*4402, B*2705, B*1402, and B*0702 on the surface of disease cells. They are envisioned to among other things (a) stimulate an immune response to the proliferative disease, e.g., cancer, (b) to function as immunotherapeutics in adoptive T cell therapy or as a vaccine, (c) facilitate antibody recognition of tumor boundaries in surgical pathology samples, (d) act as biomarkers for early detection and/or diagnosis of the disease, and (e) act as targets in the generation antibody-like molecules which recognize the target-peptide/MHC complex.

The invention relates to multi-epitopic peptide compounds obtained from PSA, HwB and LmLRAB proteins of Leishmania as well as to pharmaceutical compositions and vaccines for use against one or more leishmaniases.

The invention relates to immunogenic compositions comprising an antigen obtained or derived from an antigenic epitope of one or more pathogens that induces an immune response in a mammal, an antigen obtained or derived from bacterial cell wall or viral material that induces an immune response in a mammal such as LTA, PNG or LPS, and a T cell stimulating antigen such as CRM. Preferably the immunogenic composition is a vaccine that is effective against a pathogenic infection or can generate antibodies that can be collected that are protective against infection by the pathogen. In addition, the invention relates to vaccines comprising antigens and to method for treating and preventing an infection.

Embodiments herein relate to compositions and methods for stabilizing Flaviviruses. In certain embodiments, compositions and methods disclosed herein concern stabilizing live, attenuated or unattenuated (e.g. live whole) flaviviruses. Other embodiments relate to compositions and methods for reducing degradation of live, attenuated or unattenuated flaviviruses. Other embodiments relate to improved formulations for prolonging stabilization of live attenuated or unattenuated Flaviviruses during manufacturing, storage, accelerated storage and transport. Yet other embodiments relate to uses of compositions disclosed herein in kits for transportable applications and methods.

Aspects of the disclosure relate to compositions and methods for eliciting (or enhancing) anti-repeat-associated non-ATG (RAN) protein antibody expression or production in a subject. Administration of the compositions according to the methods of the present disclosure may in some embodiments result in decreased levels of RAN protein expression and/or aggregation. Such compositions and methods may therefore be useful for the treatment of diseases and disorders known to be associated with RAN proteins.

Described herein are antiviral peptides, polynucleotides encoding the peptides, and compositions containing the peptides. Furthermore, described herein are methods for using the peptides, polynucleotides, and compositions for treating or inhibiting a viral infection or one or more symptoms of a viral infection.

Modified alphaviruses encoding a SARS-CoV-2 spike protein or antigenic segment of the SARS-CoV-2 spike protein are provided. The modified alphaviruses include replicative defective Sindbis viruses. The modified viruses express or are administered with an immunomodulatory agent that is an agonist antibody or antigenbinding fragment thereof, or a cytokine, or a combination thereof. Pharmaceutical compositions that include the modified alphaviruses and methods of using the modified alphaviruses and compositions that contain them are provided. The compositions are used to stimulate a therapeutic or protective effect against SARS-CoV-2 infection that includes humoral and cell mediated responses.