Abstract: The present disclosure provides a lipid nanoparticle comprising encapsulated mRNA and at least 30 mol % of a sphingolipid (e.g. sphingomyelin (SM)), and at least one of a sterol and a hydrophilic polymer-lipid conjugate, the lipid nanoparticle comprising a core comprising an electron dense region and an aqueous portion surrounded at least partially by a lipid layer comprising a bilayer and the lipid nanoparticle exhibiting at least a 2-fold increase in gene expression in the liver, spleen and/or bone marrow at 4 or 24 hours post-injection as compared to a lipid nanoparticle encapsulating mRNA with an Onpattro™-type formulation of cationic, ionizable lipid/DSPC or ESM/cholesterol/PEG-lipid at 50/10/38.5/1.5, mol:mol, wherein the gene expression is measured in an animal model by detection of green fluorescent protein (GFP). Further provided are methods of medical treatment and uses of such lipid nanoparticles to treat or prevent a disease condition in a hepatic or non-hepatic tissue or organ.

Abstract: Compositions for and methods of stimulating a MHC I mediated immune response comprising stimulating MHC I endolysosomal cross presentation in dendritic cells. Stimulation MHC I endolysosomal cross presentation may comprise over-expression CD74 in dendritic cells and/or targeting antigens to the MHC I endolysosomal cross presentation pathway. Fusion proteins comprising an antigen or fragment thereof and a CD74 endolysosomal targeting sequence are also provided.

Abstract: A vaccine composition for combating Pox viridae viral infections in living organisms such as mammals (including humans) comprises TAP-1 and/or TAP-2 to augment the antigen processing capability of infected cells and hence their immunogenicity. The composition may be used alone or, preferably, as an immunogenicity-enhancing adjuvant with a pox antigen-based vaccine, especially in the treatment or prophylaxis of viral infections such as smallpox.

Abstract: A vaccine composition for combating Pox viridae viral infections in living organisms such as mammals (including humans) comprises TAP-1 and/or TAP-2 to augment the antigen processing capability of infected cells and hence their immunogenicity. The composition may be used alone or, preferably, as an immunogenicity-enhancing adjuvant with a pox antigen-based vaccine, especially in the treatment or prophylaxis of viral infections such as smallpox.

Abstract: A vaccine composition for combating Pox viridae viral infections in living organisms such as mammals (including humans) comprises TAP-1 and/or TAP-2 to augment the antigen processing capability of infected cells and hence their immunogenicity. The composition may be used alone or, preferably, as an immunogenicity-enhancing adjuvant with a pox antigen-based vaccine, especially in the treatment or prophylaxis of viral infections such as smallpox.