A nonadjuvanted polypeptide nanoparticle vaccine confers long-lasting protection against rodent malaria.

We have designed and produced a prototypic malaria vaccine based on a highly versatile self-assembling polypeptide nanoparticle (SAPN) platform that can repetitively display antigenic epitopes. We used this platform to display a tandem repeat of the B cell immunodominant repeat epitope (DPPPPNPN)(2)D of the malaria parasite Plasmodium berghei circumsporozoite protein. Administered in saline, without the need for a heterologous adjuvant, the SAPN construct P4c-Mal conferred a long-lived, protective immune response to mice with a broad range of genetically distinct immune backgrounds including the H-2(b), H-2(d), and H-2(k) alleles. Immunized mice produced a CD4(+) T cell-dependent, high-titer, long-lasting, high-avidity Ab response against the B cell epitope. Mice were protected against an initial challenge of parasites up to 6 mo after the last immunization or for up to 15 mo against a second challenge after an initial challenge of parasites had successfully been cleared. Furthermore, we demonstrate that the SAPN platform not only functions to deliver an ordered repetitive array of B cell peptide epitopes but operates as a classical immunological carrier to provide cognate help to the P4c-Mal-specific B cells.

Structure-based design of peptides that self-assemble into regular polyhedral nanoparticles.

Artificial particulate systems such as polymeric beads and liposomes are being applied in drug delivery, drug targeting, antigen display, vaccination, and other technologies. Here we used computer modeling to design a novel type of nanoparticles composed of peptides as building blocks. We verified the computer models via solid-phase peptide synthesis and biophysical analyses. We describe the structure-based design of a novel type of nanoparticles with regular polyhedral symmetry and a diameter of about 16 nm, which self-assembles from single polypeptide chains. Each peptide chain is composed of two coiled coil oligomerization domains with different oligomerization states joined by a short linker segment. In aqueous solution the peptides form nanoparticles of about 16 nm diameter. Such peptide nanoparticles are ideally suited for medical applications such as drug targeting and drug delivery systems, such as imaging devices, or they may be used for repetitive antigen display.

Nanoscale assemblies and their biomedical applications.

Nanoscale assemblies are a unique class of materials, which can be synthesized from inorganic, polymeric or biological building blocks. The multitude of applications of this class of materials ranges from solar and electrical to uses in food, cosmetics and medicine. In this review, we initially highlight characteristic features of polymeric nanoscale assemblies as well as those built from biological units (lipids, nucleic acids and proteins). We give special consideration to protein nanoassemblies found in nature such as ferritin protein cages, bacterial microcompartments and vaults found in eukaryotic cells and designed protein nanoassemblies, such as peptide nanofibres and peptide nanotubes. Next, we focus on biomedical applications of these nanoscale assemblies, such as cell targeting, drug delivery, bioimaging and vaccine development. In the vaccine development section, we report in more detail the use of virus-like particles and self-assembling polypeptide nanoparticles as new vaccine delivery platforms.