Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses

Betacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and the SARS-CoV-2 pandemic1–4. Vaccines that elicit protective immunity against SARS-CoV-2 and betaCoVs circulating in animals have the potential to prevent future betaCoV pandemics. Here, we show that macaque immunization with a multimeric SARS-CoV-2 receptor binding domain (RBD) nanoparticle adjuvanted with 3M-052/Alum elicited cross-neutralizing antibody (cross-nAb) responses against batCoVs, SARS-CoV-1, SARS-CoV-2, and SARS-CoV-2 variants B.1.1.7, P.1, and B.1.351. Nanoparticle vaccination resulted in a SARS-CoV-2 reciprocal geometric mean neutralization ID50 titer of 47,216, and protection against SARS-CoV-2 in macaque upper and lower respiratory tracts. Importantly, nucleoside-modified mRNA encoding a stabilized transmembrane spike or monomeric RBD also induced SARS-CoV-1 and batCoV cross-nAbs, albeit at lower titers. These results demonstrate current mRNA vaccines may provide some protection from future zoonotic betaCoV outbreaks, and provide a platform for further development of pan-betaCoV vaccines

Particles-vortex interactions and flow visualization in He4

Recent experiments have demonstrated a remarkable progress in implementing and use of the Particle Image Velocimetry (PIV) and particle tracking techniques for the study of turbulence in He4. However, an interpretation of the experimental data in the superfluid phase requires understanding how the motion of tracer particles is affected by the two components, the viscous normal fluid and the inviscid superfluid. Of a particular importance is the problem of particle interactions with quantized vortex lines which may not only strongly affect the particle motion, but, under certain conditions, may even trap particles on quantized vortex cores. The article reviews recent theoretical, numerical, and experimental results in this rapidly developing area of research, putting critically together recent results, and solving apparent inconsistencies. Also discussed is a closely related technique of detection of quantized vortices negative ion bubbles in He4.Comment: To appear in the J Low Temperature Physic

Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine

Coronavirus vaccines that are highly effective against current and anticipated SARS-CoV-2 variants are needed to control COVID-19. We previously reported a receptor-binding domain (RBD)-sortase A-conjugated ferritin nanoparticle (scNP) vaccine that induced neutralizing antibodies against SARS-CoV-2 and pre-emergent sarbecoviruses and protected non-human primates (NHPs) from SARS-CoV-2 WA-1 infection. Here, we find the RBD-scNP induced neutralizing antibodies in NHPs against pseudoviruses of SARS-CoV and SARS-CoV-2 variants including 614G, Beta, Delta, Omicron BA.1, BA.2, BA.2.12.1, and BA.4/BA.5, and a designed variant with escape mutations, PMS20. Adjuvant studies demonstrate variant neutralization titers are highest with 3M-052-aqueous formulation (AF). Immunization twice with RBD-scNPs protect NHPs from SARS-CoV-2 WA-1, Beta, and Delta variant challenge, and protect mice from challenges of SARS-CoV-2 Beta variant and two other heterologous sarbecoviruses. These results demonstrate the ability of RBD-scNPs to induce broad neutralization of SARS-CoV-2 variants and to protect animals from multiple different SARS-related viruses. Such a vaccine could provide broad immunity to SARS-CoV-2 variants

A Proposed Information Architecture for Telehealth System Interoperability

Telemedicine technology is rapidly evolving. Whereas early telemedicine consultations relied primarily on video conferencing, consultations today may utilize video conferencing, medical peripherals, store-and-forward capabilities, electronic patient record management software, and/or a host of other emerging technologies. These remote care systems rely increasingly on distributed, collaborative information technology during the care delivery process, in its many forms. While these leading-edge systems are bellwethers for highly advanced telemedicine, the remote care market today is still immature. Most telemedicine systems are custom-designed and do not interoperate with other commercial offerings. Users are limited to a set of functionality that a single vendor provides and must often pay high prices to obtain this functionality, since vendors in this marketplace must deliver entire systems in order to compete. Besides increasing corporate research and development costs, this inhibits the ability of the user to make intelligent purchasing decisions regarding best-of-breed technologies. We propose a secure, object-oriented information architecture for telemedicine systems that promotes plug-and-play interaction between system components through standardized interfaces, communication protocols, messaging formats, and data definitions. In this architecture, each component functions as a black box, and components plug together in a lego-like fashion to achieve the desired device or system functionality. The architecture will support various ongoing standards work in the medical device arena

Criteria for environmentally associated autoimmune diseases

Increasing evidence supports a role for the environment in the development of autoimmune diseases, as reviewed in the accompanying three papers from the National Institute of Environmental Health Sciences Expert Panel Workshop. An important unresolved issue, however, is the development of criteria for identifying autoimmune disease phenotypes for which the environment plays a causative role, herein referred to as environmentally associated autoimmune diseases. There are several different areas in which such criteria need to be developed, including: 1) identifying the necessary and sufficient data to define environmental risk factors for autoimmune diseases meeting current classification criteria; 2) establishing the existence of and criteria for new environmentally associated autoimmune disorders that do not meet current disease classification criteria; and 3) identifying in clinical practice specific environmental agents that induce autoimmune disease in individual patients. Here we discuss approaches that could be useful for developing criteria in these three areas, as well as factors that should be considered in evaluating the evidence for criteria that can distinguish individuals with such disorders from individuals without such disorders with high sensitivity and specificity. Current studies suggest that multiple lines of complementary evidence will be important and that in many cases there will be clinical, serologic, genetic, epigenetic, and/or other laboratory features that could be incorporated as criteria for environmentally associated autoimmune diseases to improve diagnosis and treatment and possibly allow for preventative strategies in the future