title: Optimizing the design of protein nanoparticles as carriers for vaccine applications.
abstract: Successful vaccine development remains a huge challenge for infectious diseases such as malaria, HIV and influenza. As a novel way to present antigenic epitopes to the immune system, we have developed icosahedral self-assembling protein nanoparticles (SAPNs) to serve as a prototypical vaccine platform for infectious diseases. Here we examine some biophysical factors that affect the self-assembly of these nanoparticles, which have as basic building blocks coiled-coil oligomerization domains joined by a short linker region. Relying on in silico computer modeling predictions, we selected five different linker regions from the RCSB protein database that connect oligomerization domains, and then further studied the self-assembly and stability of in vitro produced nanoparticles through biophysical characterization of formed particles. One design in particular, T2i88, revealed excellent self-assembly and homogeneity thus paving the way toward a more optimized nanoparticle for vaccine applications.
  
  
  BACKGROUND
  Despite the widespread use of vaccines worldwide, successful development of vaccines against some diseases remains a challenge still. In this article, the authors investigated the physic-chemical and biological properties of icosahedral self-assembling protein nanoparticles (SAPNs), which mimic viral particles, in order to utilize this technology as potential platform for future design of vaccines.
authors.affiliation: Institute of Materials Science, University of Connecticut, Storrs, CT, USA.
authors.forename: Tais A P F
authors.initials: TA
authors.lastname: Doll
authors.affiliation: Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Neef
authors.affiliation: Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA.
authors.forename: Nha
authors.initials: N
authors.lastname: Duong
authors.affiliation: Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, MD, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Lanar
authors.affiliation: Center for Cellular Imaging and Nano Analytics (C-CINA), Biozentrum, University of Basel, Mattenstrasse 26, Basel, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ringler
authors.affiliation: Center for Cellular Imaging and Nano Analytics (C-CINA), Biozentrum, University of Basel, Mattenstrasse 26, Basel, Switzerland.
authors.forename: Shirley A
authors.initials: SA
authors.lastname: Müller
authors.affiliation: Institute of Materials Science, University of Connecticut, Storrs, CT, USA; Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA. Electronic address: peter.burkhard@uconn.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Burkhard
mesh_terms: D003198:Computer Simulation; D030562:Databases, Protein; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control; D008288:Malaria / Q000276:immunology / Q000517:prevention & control; D053758:Nanoparticles / Q000627:therapeutic use*; D011506:Proteins / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D014612:Vaccines / Q000276:immunology* / Q000627:therapeutic use
chemical_list: D011506:Proteins; D014612:Vaccines
keywords: Malaria; Protein design; Protein nanoparticle; Self-assembly; Vaccine carrier