Provided herein are multifunctional heteromer proteins. In specific embodiments is a heteromultimer that comprises: at least two monomeric proteins, wherein each monomeric protein comprises at least one cargo polypeptide, attached to a transporter polypeptide, such that said monomeric proteins associate to form the heteromultimer. These therapeutically novel molecules comprise monomers that function as scaffolds for the conjugation or fusion of therapeutic molecular entities resulting in the creation of bispecific or multivalent molecular species.

The present invention relates to the provision of novel immunogens comprising an antigenic PCSK9 peptide linked to an immunogenic carrier for the prevention, treatment or alleviation of PCSK9-mediated disorders. The invention further relates to methods for production of these medicaments, immunogenic compositions and pharmaceutical compositing thereof and their use in medicine.

A vaccine is disclosed that promotes CD4+ T cell-independent host defense mechanisms to defend against infection by fungi such as Pneumocystis spp. The vaccine may be used to prevent or to treat fungal infections. The novel vaccine can provide protective immunity, even for immunocompromised individuals such as HIV patients having reduced levels of CD4+ T cells.

The invention belongs to the biopharmaceutical. It involves the role and mechanism of PCSK9 in inflammatory immune diseases, and the application of PCSK9 inhibitors to the preparation of drugs for the treatment of inflammatory immune diseases mediated by T cells. In particular, it involves the use of PCSK9 monoclonal antibody, PCSK9 interference RNA and PCSK9 small molecule inhibitors for treating psoriasis, atopic dermatitis, or urticaria. The invention uses psoriasis as an embodiment for the study of inflammatory and immune diseases. It is found that PCSK9 plays an important role in the treatment of inflammatory immune diseases. The PCSK9 monoclonal antibody, PCSK9 interference RNA, and PCSK9 small molecule inhibitor can be further developed for treating inflammatory immune-diseases, such as psoriasis with fewer adverse reactions, at low cost, and with good efficacy.

The present embodiments provide methods, compounds, and compositions useful for inhibiting PCSK9 expression, which may be useful for treating, preventing, or ameliorating a disease associated with PCSK9.

The present invention relates to a vaccine capable to induce the formation of antibodies directed to PCSK9 in vivo.

The present disclosure describes the grafting of epitope residues from human PCSK9 to non-human PCSK9 or PCSK9 structural homologs and elimination of 9-mers oligopeptides that are found in human protein to reduce self-targeting response. Anti-genicity of the epitope-scaffold constructs was demonstrated toward anti-human PCSK9 antibodies. similar to wild type human PCSK9. It was shown that disclosed PCSK9 immunogens could significantly reduce LDL and cholesterol levels in immunized mice.

This invention relates to methods for increasing the efficiency of siRNA administrations via pre-administration of an agent that lowers LDL receptor levels.

The present invention relates to PCSK9 inhibitors and methods of use thereof. Specifically, the invention relates to PCSK9 cell-based assay, PCSK9 inhibiting polypeptides and derivatives thereof. The invention includes pharmaceutical compositions comprising a PCSK9 inhibitor polypeptide together with a pharmaceutically acceptable carrier and method for treating cardiovascular disorders, inflammatory diseases or inflammatory response to infection.

The present invention relates to a vaccine capable to induce production of antibodies directed to PCSK9 in vivo.