Quantifying Nanoscale Properties Of Engineered Virus Capsids For Malaria Vaccines

An important challenge in targeted drug delivery and vaccine development is to create the most effective interface between the carrier and target cells. Parasitic diseases, for which no approved vaccines are available, remain a world health problem with over one million severe cases per year attributed to malaria alone. In parallel to developing potential malaria antigen constructs (1), we have also bioengineered and characterized nanoscale virus-like particles (VLPs) with tools such as atomic force microscopy (AFM) and quantitative nanomechanical mapping (QNM) in hopes that these might serve as possible carriers for drugs or vaccines because of how they uniquely interact with human cells. Through using AFM and QNM techniques we have revealed some morphological features of our own bioengineered VLP, a protein capsid of bacteriophage Qβ (d = 25 nm), and analyzed deformation of the capsid under compressive force to quantify its elastic properties. We have found that these particles exhibit a linear relationship between compressive force and deformation as would a Hookean spring. Significant deformation (u003e 5 nm) was observed at forces of 0.1 - 0.5 nN. Our calculated spring constant for our Qβ capsid, 0.059 N/m, indicates that our VLP is more pliable than others of similar protein structure, which is possibly a favorable characteristic for the capsid to bind with the cell membrane in an in vivo carrier scenario. We are also using this analytical technique for the characterization of chemically conjugated (malaria) vaccines. Ref (1) “Development of a Pfs25-EPA malaria transmission blocking vaccine as a chemically conjugated nanoparticle.” Shimp RL Jr, Rowe C, Reiter K, Chen B, Nguyen V, Aebig J, Rausch KM, Kumar K, Wu Y, Jin AJ, Jones DS, Narum DL. Vaccine. 2013. 31:2954-62. doi: 10.1016/j.vaccine.2013.04.034.