The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.

The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.

Disclosed herein are circular RNAs and transfer vehicles, along with related compositions and methods of treatment. The circular RNAs can comprise group I intron fragments, spacers, an IRES, duplex forming regions, and/or an expression sequence, thereby having the features of improved expression, functional stability, low immunogenicity, ease of manufacturing, and/or extended half-life compared to linear RNA. Pharmaceutical compositions comprising such circular RNAs and transfer vehicles are particularly suitable for efficient protein expression in immune cells in vivo. Also disclosed are precursor RNAs and materials useful in producing the precursor or circular RNAs, which have improved circularization efficiency and/or are compatible with effective circular RNA purification methods.

The present inventors have found that innate immune response and T cell exhaustion pathway are more greatly over-expressed in pigs than cattle, such that the pigs are less likely to form adaptive and humoral immune responses than cattle. It would be suggested herein an innovative strategy for improvement of abnormal immune responses in pigs by simultaneously inducing potent cellular and humoral immune responses and applying T cell agonists as a new vaccine adjuvant. This result may provide an important clue for understanding a difference in the immune response between the cattle and pigs, while suggesting a method for maximizing the immune response and vaccine efficacy, which are less expressed in pigs than cattle.

The present inventors have found that innate immune response and T cell exhaustion pathway are more greatly over-expressed in pigs than cattle, such that the pigs are less likely to form adaptive and humoral immune responses than cattle. It would be suggested herein an innovative strategy for improvement of abnormal immune responses in pigs by simultaneously inducing potent cellular and humoral immune responses and applying T cell agonists as a new vaccine adjuvant. This result may provide an important clue for understanding a difference in the immune response between the cattle and pigs, while suggesting a method for maximizing the immune response and vaccine efficacy, which are less expressed in pigs than cattle.

Provided is an immunostimulator containing: chitosan and/or a chitosan derivative each having a weight-average molecular weight of 10k to 1000k; and an anionic surfactant, the immunostimulator being in particulate form. Also provided are a pharmaceutical composition and an alimentary product, each containing the immunostimulator as an active ingredient.

Described herein are Zika virus vaccines and compositions and methods of producing and administering said vaccines to subjects in need thereof.

Described herein are Zika virus vaccines and compositions and methods of producing and administering said vaccines to subjects in need thereof.

Disclosed is a new class of conjugated virus-like particles (VLPs). These conjugated VLPs bind a wide variety of tumors and comprise epitopes recognized by a prior T cell immune response already existing in a host. These epitopes are derived from pathogens or previous vaccinations (such as early childhood vaccines). This provokes the body's pre-existing cytotoxic immunity obtained through previous infection or previous childhood vaccination to be redirected to the tumor cells for the elimination of cancer, and form long-term anti-tumor immunity. The described conjugated VLPs are useful for tailoring a broad range of tumors towards a response from existing immunity circumventing the need to identify tumor antigens or generate tumor-specific immune responses. Importantly, the compositions and methods described herein broadens opportunities for treatment for all cancer types in subjects who previously had un-targetable cancers due to various technological and biological limitations of currently available immuno-therapeutic drugs.

The present invention relates to single dose parenteral vaccine compositions comprising mixtures of monovalent Norovirus virus-like particles. Methods of conferring protective immunity against Norovirus infections in a human subject by administering such compositions are also disclosed.