A model cytotoxic T‐cell epitope is linked to a synthetic lipid tail, forming a peptide amphiphile that self‐assembles into cylindrical micelles. The micelles are capable of inducing a cytotoxic T‐cell response in mice that slows the growth of tumors expressing the tumor antigen.

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Considerable success has been made with many peptide antigen formulations, and peptide-based vaccines are emerging as the next generation of prophylactic and remedial immunotherapy. However, finding an optimal platform balancing all of the requirements for an effective, specific and safe immune response remains a major challenge for many infectious and chronic diseases. This review outlines how peptide immunogenicity is influenced by the way in which peptides are presented to the immune system, underscoring the need for multifunctional delivery systems that couple antigen and adjuvant into a single construct. Particular attention is given to the ability of Toll-like receptor agonists to act as adjuvants. A survey of recent approaches to developing peptide antigen delivery systems is given, many of which incorporate Toll-like receptor agonists into the design.

Recently, kinesin biomolecular motors and microtubules filaments (MTs) were used to transport metal and semiconductor nanoparticles with the long-term goal of exploiting this active transport system to dynamically assemble nanostructured materials. In some cases, however, the presence of nanoparticle cargo on MTs was shown to inhibit transport by interfering with kinesin-MT interactions. The primary objectives of this work were (1) to determine what factors affect the ability of kinesin and MTs to transport nanoparticle cargo, and (2) to establish a functional parameter space in which kinesin and MTs can support unimpeded transport of nanoparticles and materials. Of the factors evaluated, nanoparticle density on a given MT was the most significant factor affecting kinesin-based transport of nanoparticles. The density of particles was controlled by limiting the number of available linkage sites (i.e., biotinylated tubulin), and/or the relative concentration of nanoparticles in solution. Nanoparticle size was also a significant factor affecting transport, and attributed to the ability of particles < 40 nm in diameter to bind to the "underside" of the MT, and block kinesin transport. Overall, a generalized method of assembling and transporting a range of nanoparticle cargo using kinesin and MTs was established.

Abstract. Delivery system design and adjuvant development are crucially important areas of research for improving vaccines. Peptide amphiphile micelles are a class of biomaterials that have the unique potential to function as both vaccine delivery vehicles and self-adjuvants. In this study, peptide amphiphiles comprised of a group A streptococcus B cell antigen (J8) and a dialkyl hydrophobic moiety (diC 16 ) were synthesized and organized into self-assembled micelles, driven by hydrophobic interactions among the alkyl tails. J8-diC 16 formed cylindrical micelles with highly α-helical peptide presented on their surfaces. Both the micelle length and secondary structure were shown to be enhanced by annealing. When injected into mice, J8-diC 16 micelles induced a strong IgG1 antibody response that was comparable to soluble J8 peptide supplemented with two classical adjuvants. It was discovered that micelle adjuvanticity requires the antigen be a part of the micelle since separation of J8 and the micelle was insufficient to induce an immune response. Additionally, the diC 16 tail appears to be non-immunogenic since it does not stimulate a pathogen recognition receptor whose agonist (Pam 3 Cys) possesses a very similar chemical structure. The research presented in this paper demonstrates the promise peptide amphiphile micelles have in improving the field of vaccine engineering.

Inducing a strong and specific immune response is the hallmark of a successful vaccine. Nanoparticles have emerged as promising vaccine delivery devices to discover and elicit immune responses. Fine-tuning a nanoparticle vaccine to create an immune response with specific antibody and other cellular responses is influenced by many factors such as shape, size, and composition. Peptide amphiphile micelles are a unique biomaterials platform that can function as a modular vaccine delivery system, enabling control over many of these important factors and delivering payloads more efficiently to draining lymph nodes. In this study, the modular properties of peptide amphiphile micelles are utilized to improve an immune response against a Group A Streptococcus B cell antigen (J8). The hydrophobic/hydrophilic interface of peptide amphiphile micelles enabled the precise entrapment of amphiphilic adjuvants which were found to not alter micelle formation or shape. These heterogeneous micelles significantly enhanced murine antibody responses when compared to animals vaccinated with nonadjuvanted micelles or soluble J8 peptide supplemented with a classical adjuvant. The heterogeneous micelle induced antibodies also showed cross-reactivity with wild-type Group A Streptococcus providing evidence that micelle-induced immune responses are capable of identifying their intended pathogenic targets.

A significant challenge in utilizing kinesin biomolecular motors in integrated nanoscale systems is the ability to regulate motor function in vitro. Here we report a versatile mechanism for reversibly controlling the function of kinesin biomolecular motors independent of the fuel supply (ATP). Our approach relied on inhibiting conformational changes in the neck-linker region of kinesin, a process necessary for microtubule transport. We introduced a chemical switch into the neck-linker of kinesin by genetically engineering three histidine residues to create a Zn(2+)-binding site. Gliding motility of microtubules by the mutant kinesin was successfully inhibited by >/=10 microM Zn(2+), as well as other divalent metals. Motility was successfully restored by removal of Zn(2+) using a number of different chelators. Lastly, we demonstrated the robust and cyclic nature of the switch using sequential Zn(2+)/chelator additions. Overall, this approach to controlling motor function is highly advantageous as it enables control of individual classes of biomolecular motors while maintaining a consistent level of fuel for all motors in a given system or device.

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