No abstract

Magnetite nanocrystals are synthesized in the presence of a recombinant Mms6 protein thought to be involved in the biomineralization of bacterial magnetite magnetosomes, the mammalian iron‐storage protein, ferritin, and two proteins not known to bind iron, lipocalin (Lcn2) and bovine serum albumin (BSA). To mimic the conditions at which magnetite nanocrystals are formed in magnetotactic bacteria, magnetite synthesis is performed in a polymeric gel to slow down the diffusion rates of the reagents. Recombinant Mms6 facilitates formation of ca. 30 nm single‐domain, uniform magnetite nanocrystals in solution, as verified by using transmission electron microscopy analysis and magnetization measurements. The nanocrystals formed in the presence of ferritin, Lcn2, and BSA, do not exhibit the uniform sizes and shapes observed for those produced in the presence of Mms6. Mms6‐derived magnetite nanoparticles show the largest magnetization values above the blocking temperature, as well as the largest magnetic susceptibility compared to those of the nanomaterials synthesized with other proteins. The latter is indicative of a substantial effective magnetic moment per particle, which is consistent with the presence of magnetite with a well‐defined crystalline structure. The combination of electron microscopy analysis and magnetic measurements confirms our hypothesis that Mms6 promotes the shape‐selective formation of uniform superparamagnetic nanocrystals. This provides a unique bioinspired route for synthesis of uniform magnetite nanocrystals.

We have designed a new synthesis route to create polyanhydrides based on monomers that contain hydrophilic entities within highly hydrophobic backbones. The method results in polyanhydrides that can be easily processed into drug-containing tablets. The synthesis, characterization, and erosion studies of polyanhydride copolymers based on 1,6-bis(p-carboxyphenoxy)hexane (CPH), which is highly hydrophobic, and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG), which has hydrophilic oligomeric ethylene glycol segments in the monomer unit, was performed using a combination of molecular spectroscopy, thermal analysis, gravimetry, and scanning electron microscopy. The studies demonstrate that by increasing the CPH content in the CPTEG:CPH copolymers, the erosion of the system can be tailored from bulk-eroding to surface-eroding mechanism. These systems have promise as protein carriers.

Despite the successes provided by vaccination, many challenges still exist with respect to controlling new and re-emerging infectious diseases. Innovative vaccine platforms composed of adaptable adjuvants able to appropriately modulate immune responses, induce long-lived immunity in a single dose, and deliver immunogens in a safe and stable manner via multiple routes of administration are needed. This work describes the development of a novel biodegradable polyanhydride nanoparticle-based vaccine platform administered as a single intranasal dose that induced long-lived protective immunity against respiratory disease caused by Yesinia pestis, the causative agent of pneumonic plague. Relative to the responses induced by the recombinant protein F1-V alone and MPLA-adjuvanted F1-V, the nanoparticle-based vaccination regimen induced an immune response that was characterized by high titer and high avidity IgG1 anti-F1-V antibody that persisted for at least 23 weeks post-vaccination. After challenge, no Y. pestis were recovered from the lungs, livers, or spleens of mice vaccinated with the nanoparticle-based formulation and histopathological appearance of lung, liver, and splenic tissues from these mice post-vaccination was remarkably similar to uninfected control mice.

For humans, companion animals, and food producing animals, vaccination has been touted as the most successful medical intervention for the prevention of disease in the twentieth century. However, vaccination is not without problems. With the development of new and less reactogenic vaccine antigens, which take advantage of molecular recombinant technologies, also comes the need for more effective adjuvants that will facilitate the induction of adaptive immune responses. Furthermore, current vaccine adjuvants are successful at generating humoral or antibody mediated protection but many diseases currently plaguing humans and animals, such as tuberculosis and malaria, require cell mediated immunity for adequate protection. A comprehensive discussion is presented of current vaccine adjuvants, their effects on the induction of immune responses, and vaccine adjuvants that have shown promise in recent literature.