Stalking influenza by vaccination with pre-fusion headless HA mini-stem

Inaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies indudced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity.

An out-of-plane linear motion measurement system based on optical beam deflection

Measurement of out-of-plane linear motion with high precision and bandwidth is indispensable for development of precision motion stages and for dynamic characterization of mechanical structures. This paper presents an optical beam deflection (OBD) based system for measurement of out-of-plane linear motion for fully reflective samples. The system also achieves nearly zero cross-sensitivity to angular motion, and a large working distance. The sensitivities to linear and angular motion are analytically obtained and employed to optimize the system design. The optimal shot-noise limited resolution is shown to be less than one angstrom over a bandwidth in excess of 1 kHz. Subsequently, the system is experimentally realized and the sensitivities to out-of-plane motions are calibrated using a novel strategy. The linear sensitivity is found to be in agreement with theory. The angular sensitivity is shown to be over 7.5-times smaller than that of conventional OBD. Finally, the measurement system is employed to measure the transient response of a piezo-positioner, and, with the aid of an open-loop controller, reduce the settling time by about 90%. It is also employed to operate the positioner in closed-loop and demonstrate significant minimization of hysteresis and positioning error.