Andreas M. Reichmuth

The induction of a strong cytotoxic T cell response is an important prerequisite for successful immunotherapy against many viral diseases and tumors. Nucleotide vaccines, including mRNA vaccines with their intracellular antigen synthesis, have been shown to be potent activators of a cytotoxic immune response. The intracellular delivery of mRNA vaccines to the cytosol of antigen presenting immune cells is still not sufficiently well understood. Here, we report on the development of a lipid nanoparticle formulation for the delivery of mRNA vaccines to induce a cytotoxic CD 8 T cell response. We show transfection of dendritic cells, macrophages, and neutrophils. The efficacy of the vaccine was tested in an aggressive B16F10 melanoma model. We found a strong CD 8 T cell activation after a single immunization. Treatment of B16F10 melanoma tumors with lipid nanoparticles containing mRNA coding for the tumor-associated antigens gp100 and TRP2 resulted in tumor shrinkage and extended the overall survival of the treated mice. The immune response can be further increased by the incorporation of the adjuvant LPS. In conclusion, the lipid nanoparticle formulation presented here is a promising vector for mRNA vaccine delivery, one that is capable of inducing a strong cytotoxic T cell response. Further optimization, including the incorporation of different adjuvants, will likely enhance the potency of the vaccine.

mRNA vaccines elicit a potent immune response including antibodies and cytotoxic T cells. mRNA vaccines are currently evaluated in clinical trials for cancer immunotherapy applications, but also have great potential as prophylactic vaccines. Efficient delivery of mRNA vaccines will be key for their success and translation to the clinic. Among potential nonviral vectors, lipid nanoparticles are particularly promising. Indeed, lipid nanoparticles can be synthesized with relative ease in a scalable manner, protect the mRNA against degradation, facilitate endosomal escape, can be targeted to the desired cell type by surface decoration with ligands, and as needed, can be codelivered with adjuvants.

Inelastic helium-atom scattering from epitaxial films (2--20 monolayers) of sodium on Cu(001) reveals a large number of nearly dispersionless phonon modes whose frequencies depend on the thickness and scale as the lower harmonics of an open-ended organ pipe. These data provide evidence for confined acoustic resonances, corresponding to longitudinal standing waves normal to the surface with frequencies about 20% larger than in the bulk.

Breathable and waterproof membranes that self-seal damaged areas are prepared by modifying a poly(ether ester) membrane with an amphiphilic polymer co-network. The latter swells in water and the gel closes punctures. Damaged composite membranes remain water tight up to pressures of at least 1.6 bar. This material is useful for applications where water-vapor permeability, self-sealing properties, and waterproofness are desired, as demonstrated for a medical cooling device. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Inelastic helium-atom scattering from Cu(001) shows giant intensities for the longitudinal-surface-phonon resonance. This effect, most pronounced in the 〈100〉 direction and not visible with electron-energy-loss spectroscopy, indicates a very large anisotropic deformability of conduction electrons against the longitudinal modes of surface atoms. Its size and anisotropy are well accounted for by a pseudocharge model for surface dynamics.