A computationally designed antigen eliciting broad humoral responses against SARS-CoV-2 and related sarbecoviruses

The threat of spillovers of coronaviruses associated with the severe acute respiratory syndrome (SARS) from animals to humans necessitates vaccines that offer broader protection from sarbecoviruses. By leveraging a viral-genome-informed computational method for selecting immune-optimized and structurally engineered antigens, here we show that a single antigen based on the receptor binding domain of the spike protein of sarbecoviruses elicits broad humoral responses against SARS-CoV-1, SARS-CoV-2, WIV16 and RaTG13 in mice, rabbits and guinea pigs. When administered as a DNA immunogen or by a vector based on a modified vaccinia virus Ankara, the optimized antigen induced vaccine protection from the Delta variant of SARS-CoV-2 in mice genetically engineered to express angiotensin-converting enzyme 2 and primed by a viral-vector vaccine (AZD1222) against SARS-CoV-2. A vaccine formulation incorporating mRNA coding for the optimized antigen further validated its broad immunogenicity. Vaccines that elicit broad immune responses across subgroups of coronaviruses may counteract the threat of zoonotic spillovers of betacoronaviruses

Tetrazine-Triggered Bioorthogonal Cleavage of trans-Cyclooctene-Caged Phenols Using a Minimal Self-Immolative Linker Strategy

Bond-cleavage reactions triggered by bioorthogonal tetrazine ligation have emerged as strategies to chemically control the function of (bio)molecules and achieve activation of prodrugs in living systems. While most of these approaches make use of caged amines, current methods for the release of phenols are limited by unfavorable reaction kinetics or insufficient stability of the Tz-responsive reactants. To address this issue, we have implemented a self-immolative linker that enables the connection of cleavable trans-cyclooctenes (TCO) and phenols via carbamate linkages. Based on detailed investigation of the reaction mechanism with several Tz, revealing up to 96% elimination after 2 hours, we have developed a TCO-caged prodrug with 700-fold reduced cytotoxicity compared to the parent drug and achieved efficient in situ activation upon Tz/TCO click-to-release

A computationally designed antigen eliciting broad humoral responses against SARS-CoV-2 and related sarbecoviruses.

The threat of spillovers of coronaviruses associated with the severe acute respiratory syndrome (SARS) from animals to humans necessitates vaccines that offer broader protection from sarbecoviruses. By leveraging a viral-genome-informed computational method for selecting immune-optimized and structurally engineered antigens, here we show that a single antigen based on the receptor binding domain of the spike protein of sarbecoviruses elicits broad humoral responses against SARS-CoV-1, SARS-CoV-2, WIV16 and RaTG13 in mice, rabbits and guinea pigs. When administered as a DNA immunogen or by a vector based on a modified vaccinia virus Ankara, the optimized antigen induced vaccine protection from the Delta variant of SARS-CoV-2 in mice genetically engineered to express angiotensin-converting enzyme 2 and primed by a viral-vector vaccine (AZD1222) against SARS-CoV-2. A vaccine formulation incorporating mRNA coding for the optimized antigen further validated its broad immunogenicity. Vaccines that elicit broad immune responses across subgroups of coronaviruses may counteract the threat of zoonotic spillovers of betacoronaviruses

InAs-Al Hybrid Devices Passing the Topological Gap Protocol

We present measurements and simulations of semiconductor-superconductor heterostructure devices that are consistent with the observation of topological superconductivity and Majorana zero modes. The devices are fabricated from high-mobility two-dimensional electron gases in which quasi-one-dimensional wires are defined by electrostatic gates. These devices enable measurements of local and non-local transport properties and have been optimized via extensive simulations for robustness against non-uniformity and disorder. Our main result is that several devices, fabricated according to the design's engineering specifications, have passed the topological gap protocol defined in Pikulin {\it et al.}\ [arXiv:2103.12217]. This protocol is a stringent test composed of a sequence of three-terminal local and non-local transport measurements performed while varying the magnetic field, semiconductor electron density, and junction transparencies. Passing the protocol indicates a high probability of detection of a topological phase hosting Majorana zero modes. Our experimental results are consistent with a quantum phase transition into a topological superconducting phase that extends over several hundred millitesla in magnetic field and several millivolts in gate voltage, corresponding to approximately one hundred micro-electron-volts in Zeeman energy and chemical potential in the semiconducting wire. These regions feature a closing and re-opening of the bulk gap, with simultaneous zero-bias conductance peaks at {\it both} ends of the devices that withstand changes in the junction transparencies. The measured maximum topological gaps in our devices are 20-$30\,\mu$eV. This demonstration is a prerequisite for experiments involving fusion and braiding of Majorana zero modes.Comment: Fixed typos. Fig. 3 is now readable by Adobe Reade