Virus-Like Particles That Display Zika Virus Envelope Protein Domain III Induce Potent Neutralizing Immune Responses in Mice

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Description

Several Zika virus (ZIKV) vaccine candidates have recently been described which use inactivated whole virus, DNA or RNA that express the virus’ Envelope (E) glycoprotein as the antigen. These were successful in stimulating production of virus-targeted antibodies that protected animals…

Several Zika virus (ZIKV) vaccine candidates have recently been described which use inactivated whole virus, DNA or RNA that express the virus’ Envelope (E) glycoprotein as the antigen. These were successful in stimulating production of virus-targeted antibodies that protected animals against ZIKV challenges, but their use potentially will predispose vaccinated individuals to infection by the related Dengue virus (DENV). We have devised a virus like particle (VLP) carrier based on the hepatitis B core antigen (HBcAg) that displays the ZIKV E protein domain III (zDIII), and shown that it can be produced quickly and easily purified in large quantities from Nicotiana benthamiana plants. HBcAg-zDIII VLPs are shown to be highly immunogenic, as two doses elicited potent humoral and cellular responses in mice that exceed the threshold correlated with protective immunity against multiple strains of Zika virus. Notably, HBcAg-zDIII VLPs-elicited antibodies did not enhance the infection of DENV in Fc gamma receptor-expressing cells, offsetting the concern of ZIKV vaccines inducing cross-reactive antibodies and sensitizing people to subsequent DENV infection. Thus, our zDIII-based vaccine offers improved safety and lower cost production than other current alternatives, with equivalent effectiveness.

Date Created
2017-08-09
Agent

In support of high quality 3-D ultrasound imaging for hand-held devices

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Description
Three dimensional (3-D) ultrasound is safe, inexpensive, and has been shown to drastically improve system ease-of-use, diagnostic efficiency, and patient throughput. However, its high computational complexity and resulting high power consumption has precluded its use in hand-held applications.

In this dissertation,…

Three dimensional (3-D) ultrasound is safe, inexpensive, and has been shown to drastically improve system ease-of-use, diagnostic efficiency, and patient throughput. However, its high computational complexity and resulting high power consumption has precluded its use in hand-held applications.

In this dissertation, algorithm-architecture co-design techniques that aim to make hand-held 3-D ultrasound a reality are presented. First, image enhancement methods to improve signal-to-noise ratio (SNR) are proposed. These include virtual source firing techniques and a low overhead digital front-end architecture using orthogonal chirps and orthogonal Golay codes.

Second, algorithm-architecture co-design techniques to reduce the power consumption of 3-D SAU imaging systems is presented. These include (i) a subaperture multiplexing strategy and the corresponding apodization method to alleviate the signal bandwidth bottleneck, and (ii) a highly efficient iterative delay calculation method to eliminate complex operations such as multiplications, divisions and square-root in delay calculation during beamforming. These techniques were used to define Sonic Millip3De, a 3-D die stacked architecture for digital beamforming in SAU systems. Sonic Millip3De produces 3-D high resolution images at 2 frames per second with system power consumption of 15W in 45nm technology.

Third, a new beamforming method based on separable delay decomposition is proposed to reduce the computational complexity of the beamforming unit in an SAU system. The method is based on minimizing the root-mean-square error (RMSE) due to delay decomposition. It reduces the beamforming complexity of a SAU system by 19x while providing high image fidelity that is comparable to non-separable beamforming. The resulting modified Sonic Millip3De architecture supports a frame rate of 32 volumes per second while maintaining power consumption of 15W in 45nm technology.

Next a 3-D plane-wave imaging system that utilizes both separable beamforming and coherent compounding is presented. The resulting system has computational complexity comparable to that of a non-separable non-compounding baseline system while significantly improving contrast-to-noise ratio and SNR. The modified Sonic Millip3De architecture is now capable of generating high resolution images at 1000 volumes per second with 9-fire-angle compounding.
Date Created
2015
Agent
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