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Bio-Nanogolds-Emerging Hybrids For Enhanced Virus Detection And Vaccine Applications

Posted on:2014-02-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:MOHAMED SHEHATA ELMLEGY DRAZFull Text:PDF
GTID:1264330401987345Subject:Infectious diseases
Abstract/Summary:PDF Full Text Request
Hepatitis viruses are remarkable human pathogens causing a prominently increasing morbidity and mortality burden worldwide. Billions of people are infected and millions die each year. Here, we described nanogold and bio-nanogold hybrid structures for advanced detection and vaccine applications to hepatitis viruses. Briefly, we developed a hybrid nanocluster plasmonic resonator for immunological detection of hepatitis B virus (HBV). It was a preassembled plasmonic resonance nanocluster in which gold nanoparticle (AuNPs) acceptors, with HBV surface antigen epitope, and quantum dot (QD) donors with Fab antibody, are assembled into an immuno-mediated3D-oriented complex with enhanced energy transfer and fluorescence quenching. The coherent plasmonic resonance between Au and QD nanoparticles was exploited to achieve improved donor-acceptor resonance within the nanocluster, which in the presence of HBV is disassembled in a highly specific manner. The nanocluster provided high specificity and sensitivity for HBV detection, with the detection limit down to1-100viral particles per microliter or attomolar levels of HBsAg. In addition, we developed a novel nanogold-based scheme for enhanced DNA vaccine delivery against and hepatitis C virus (HCV). It involved the localized injection of nanogolds within a close vicinity to the intramuscularly applied DNA vaccine concurrently with several time-controlled electrical pulses. The metallic nature of AuNPs permitted an improved electrical conduction and cellular poration, which directly enhanced the delivery and uptake of DNA vaccine. HCV DNA vaccine of pVAX1-core and pVAX1-NS3together with varying sized AuNPs of5,50, or100nm were able to produce significantly increased levels of specific antibody and cellular immune responses than treatments with control or plasmid alone. These enhanced responses were dependent on the size and surface charge of the applied AuNPs offering a new opportunity for designing enhanced and controlled vaccine applications. Finally, both of the developed studies and the described detection and vaccine applications could be extended to other hepatitis viruses and a variety of other microbial pathogens as well.
Keywords/Search Tags:HBV, HCV, detection, DNA vaccine, immune response, antibody, gold nanoparticle, quantum dot
PDF Full Text Request
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