Engineering protein nanocages as carriers for biomedical applications

Bhaskar, Sathyamoorthy; Lim, Sierin

As each imaging modality has unique advantages such as tissue penetration depth, spatial and temporal resolution and cell specificity, the combination of multiple molecular probes of different imaging modalities will allow for more accurate diagnosis of a disease condition. To date, only near-infrared fluorescence-positron electron tomography multimodal imaging using protein nanocages has been reported, in which ferritin is used as a carrier to deliver the two imaging probes Cy5.5 and 64 Cu and a targeting ligand for imaging tumors. 65 Application of protein nanocages as vaccine/immune modulators Protein nanocages have shown promising potential as a display platform for pathogenic epitopes to elicit the production of neutralizing antibodies. HBV, HPV, influenza, HIV, hepatitis C virus, RSV, chlamydia infections and cancers such as cervical cancer and P815 tumors are a few diseases that have been targeted for vaccine development using the protein nanocage platform. [90] [91] [92] [93] Current vaccines are mostly based on whole viruses, both live attenuated and inactivated. In 1976, Edward Jenner presented the first virus-based vaccine against small pox. Since then, other vaccines have entered the market, including vaccines for hepatitis A, rubella, measles, mumps and influenza. Despite their initial success, the live attenuated viral vaccines are relatively less stable and difficult to administer. There is also the risk that these attenuated viruses will revert to their pathogenic form, which can be detrimental to the host. Neutralized virus vaccines do not carry the risk of reversion, but they are weaker, expensive and exhibit reduced vaccine coverage in a given population. To overcome this problem, subunit vaccines have been considered because they prime the immune response by the administration of a preload of viral proteins, which are often taken from the viral capsid Engineered protein cages in biomedical applications S Bhaskar and S Lim portion. Because there is no viral replication, these vaccines are safer but are less immunogenic when produced and purified without any other viral counterparts. However, the innate ability of viral capsid subunits to assemble into VLPs could be used to mimic the whole virus to improve vaccine efficacy. VLPs could also be used as a platform for displaying foreign ligands of viral or non-viral origins. 8, 92 Both enveloped and non-enveloped VLP-based vaccines have been developed. Two of the most successful non-enveloped VLP-based vaccines, namely HBV and HPV vaccines, are licensed and commercialized for clinical applications. Viruses such as influenza, hepatitis C virus and HIV can give rise to enveloped VLPs, which lack the ability to replicate. The immunogen is composed of assembled particles consisting of some or all of the surface subunits of the plasma membrane. 92 Current research is focused on the conserved epitopes of the envelope protein of HIV-1 gp-41. Developing successful HIV vaccine requires engineering different VLPs. The development of VLP-based vaccines against hepatitis C virus, filoviruses Ebola virus, Marburg virus, severe acute respiratory syndrome, coronavirus and chikungunya virus is rapidly progressing. 92, 94 Plant viruses are also used as a platform for displaying antigenic epitopes. CPMV is an extensively studied plant virus for vaccine applications. Other plant viruses include CMV and PapMV. Bacteriophage and insect virus platforms are also explored for heterologous epitop