Preclinical immunogenicity and protective efficacy of a SARS-CoV-2 RBD-based vaccine produced with the thermophilic filamentous fungal expression system Thermothelomyces heterothallica C1

INTRODUCTION: The emergency use of vaccines has been the most efficient way to control the coronavirus disease 19 (COVID-19) pandemic. However, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern has reduced the efficacy of currently used vaccines. The receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein is the main target for virus neutralizing (VN) antibodies. METHODS: A SARS-CoV-2 RBD vaccine candidate was produced in the Thermothelomyces heterothallica (formerly, Myceliophthora thermophila) C1 protein expression system and coupled to a nanoparticle. Immunogenicity and efficacy of this vaccine candidate was tested using the Syrian golden hamster (Mesocricetus auratus) infection model. RESULTS: One dose of 10-μg RBD vaccine based on SARS-CoV-2 Wuhan strain, coupled to a nanoparticle in combination with aluminum hydroxide as adjuvant, efficiently induced VN antibodies and reduced viral load and lung damage upon SARS-CoV-2 challenge infection. The VN antibodies neutralized SARS-CoV-2 variants of concern: D614G, Alpha, Beta, Gamma, and Delta. DISCUSSION: Our results support the use of the Thermothelomyces heterothallica C1 protein expression system to produce recombinant vaccines against SARS-CoV-2 and other virus infections to help overcome limitations associated with the use of mammalian expression system

LeptonInjector and LeptonWeighter: A neutrino event generator and weighter for neutrino observatories

We present a high-energy neutrino event generator, called LeptonInjector, alongside an event weighter, called LeptonWeighter. Both are designed for large-volume Cherenkov neutrino telescopes such as IceCube. The neutrino event generator allows for quick and flexible simulation of neutrino events within and around the detector volume, and implements the leading Standard Model neutrino interaction processes relevant for neutrino observatories: neutrino-nucleon deep-inelastic scattering and neutrino-electron annihilation. In this paper, we discuss the event generation algorithm, the weighting algorithm, and the main functions of the publicly available code, with examples.Comment: 28 pages, 10 figures, 3 table

Measurement of the high-energy all-flavor neutrino-nucleon cross section with IceCube

The flux of high-energy neutrinos passing through the Earth is attenuated due to their interactions with matter. The interaction rate is determined by the neutrino interaction cross section and affects the flux arriving at the IceCube Neutrino Observatory, a cubic-kilometer neutrino detector embedded in the Antarctic ice sheet. We present a measurement of the neutrino cross section between 60 TeV and 10 PeV using the high-energy starting event (HESE) sample from IceCube with 7.5 years of data. The result is binned in neutrino energy and obtained using both Bayesian and frequentist statistics. We find it compatible with predictions from the Standard Model. While the cross section is expected to be flavor independent above 1 TeV, additional constraints on the measurement are included through updated experimental particle identification (PID) classifiers, proxies for the three neutrino flavors. This is the first such measurement to use a ternary PID observable and the first to account for neutrinos from tau decay

Shoulder pain in persons with tetraplegia and the association with force application during manual wheelchair propulsion

Introduction Shoulder pain is highly prevalent in persons with spinal cord injury (Liampas et al., 2021) and restricts daily mobility and thus participation and quality of life. Shoulder loading activities, such as manual wheelchair propulsion or transfers, are seen as risk factors for shoulder pain. To minimize the risk for shoulder pain, clinical guidelines instruct persons with spinal cord injury to “use long, smooth strokes that limit high impacts on the pushrim”. Findings supporting this recommendation have been found for persons with paraplegia (Beirens et al., 2021). However, dependent on their lesion level, persons with tetraplegia do not have, full triceps function and are not able to grasp the hand rim properly, which will alter force application and may further impact shoulder pain. The aim of this study was to investigate the association between wheelchair propulsion biomechanics, including force application and spatio-temporal characteristics, and shoulder pain in persons with tetraplegia. Methods Sixteen community-dwelling, wheelchair dependent participants with tetraplegia (C7-C5, age 49.1 ±2.9 years, 23.4 ±2.4 years since injury, 94% male) were measured during wheelchair propulsion on a treadmill at two speed / power output conditions: 0.56 ms-1/10W and 0.83 ms-1/15W. A Smartwheel was fitted to the personal wheelchair to measure force application. The applied forces, their effectiveness (fraction of effective force) and smoothness (rate of rise of force, jerk), as well as push frequency, push angle and timing of the push cycles were analyzed. Based on the Wheelchair User Shoulder Pain Index (0-150), participants were stratified in groups with low (≤ 7), moderate (8-35) and high (≥ 36) shoulder pain. A mixed-effect multilevel analysis was used to identify the association between the dependent variables (propulsion biomechanics) and group of shoulder pain when controlling for sex, age, time since injury, lesion level, body weight and height. Results and Discussion The analysis showed that persons with high shoulder pain applied the force over a longer push angle (85.6°) and had a shorter recovery time (0.4s) and applied the force more effective (FEF = 40.7%) than persons with low pain (push angle = 81.2°, recovery time = 0.5s, FEF = 35.2%). In addition, persons with high shoulder pain applied less medial directed force (6.4 N) compared to persons with moderate pain (14.9 N). The results of this cross-sectional study on wheelchair propulsion in persons with tetraplegia are in contradiction to previously reported results in person with paraplegia (Beirens et al., 2021). Interestingly, tetraplegic persons with high shoulder pain are following clinical recommendation on how to propel the wheelchair optimally. These results support the importance of differentiating between lesions levels when further investigating force application as a risk factor for shoulder pain. In addition, the results ask for a close examination and possible adaptation of the clinical guidelines for persons with tetraplegia. References Beirens, B. J. H., Bossuyt, F. M., Arnet, U., van der Woude, L. H. V., & de Vries, W. H. K. (2021). Shoulder pain is associated with rate of rise and jerk of the applied forces during wheelchair propulsion in individuals with paraplegic spinal cord injury. Archives of Physical Medicine and Rehabilitation, 102(5), 856-864. https://doi.org/10.1016/j.apmr.2020.10.114 Liampas, A., Neophytou, P., Sokratous, M., Varrassi, G., Ioannou, C., Hadjigeorgiou, G. M., & Zis, P. (2021). Musculoskeletal pain due to wheelchair use: A systematic review and meta-analysis. Pain and Therapy, 10, 973-984. https://doi.org/10.1007/s40122-021-00294-

Preclinical immunogenicity and protective efficacy of a SARS-CoV-2 RBD-based vaccine produced with the thermophilic filamentous fungal expression system Thermothelomyces heterothallica C1

Introduction: The emergency use of vaccines has been the most efficient way to control the coronavirus disease 19 (COVID-19) pandemic. However, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern has reduced the efficacy of currently used vaccines. The receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein is the main target for virus neutralizing (VN) antibodies. Methods: A SARS-CoV-2 RBD vaccine candidate was produced in the Thermothelomyces heterothallica (formerly, Myceliophthora thermophila) C1 protein expression system and coupled to a nanoparticle. Immunogenicity and efficacy of this vaccine candidate was tested using the Syrian golden hamster (Mesocricetus auratus) infection model. Results: One dose of 10-μg RBD vaccine based on SARS-CoV-2 Wuhan strain, coupled to a nanoparticle in combination with aluminum hydroxide as adjuvant, efficiently induced VN antibodies and reduced viral load and lung damage upon SARS-CoV-2 challenge infection. The VN antibodies neutralized SARS-CoV-2 variants of concern: D614G, Alpha, Beta, Gamma, and Delta. Discussion: Our results support the use of the Thermothelomyces heterothallica C1 protein expression system to produce recombinant vaccines against SARS-CoV-2 and other virus infections to help overcome limitations associated with the use of mammalian expression system.</p

Das Lagemanagement des Robert Koch-Instituts während der COVID-19-Pandemie und der Austausch zwischen Bund und Ländern

The Robert Koch Institute (RKI) plays a central role in Germany in the management of health hazards of biological origin. The RKI's crisis management aims to contribute to protecting the health of the population in Germany in significant epidemic situations and to maintain the RKI's working ability over a long period of time even under high load. This article illustrates the crisis management of the RKI in general as well as during the COVID-19 pandemic. The generic RKI crisis management structures and the setup of the RKI emergency operations centre (EOC), their operationalisation in the context of the COVID-19 pandemic and the resulting challenges as of 31 October 2020 are described in this paper. The exchange between the federal and state governments during the pandemic is also described.The COVID-19 pandemic has led to extraordinary circumstances. During the epidemic situation, good communication and coordination has been essential, both within the RKI and with other federal or state authorities and expert groups. Under great pressure, the RKI produces and regularly updates recommendations, statements and assessments on various topics. To provide operational support for all COVID-19 related activities, an EOC was activated at the RKI. During the COVID-19 pandemic, there are various challenges regarding personnel and structures. It became apparent that good preparation (e.g. existing task descriptions and premises) has an important positive impact on crisis management

IceCube high-energy starting event sample : description and flux characterization with 7.5 years of data

The IceCube Neutrino Observatory has established the existence of a high-energy all-sky neutrino flux of astrophysical origin. This discovery was made using events interacting within a fiducial region of the detector surrounded by an active veto and with reconstructed energy above 60 TeV, commonly known as the high-energy starting event sample (HESE). We revisit the analysis of the HESE sample with an additional 4.5 years of data, newer glacial ice models, and improved systematics treatment. This paper describes the sample in detail, reports on the latest astrophysical neutrino flux measurements, and presents a source search for astrophysical neutrinos. We give the compatibility of these observations with specific isotropic flux models proposed in the literature as well as generic power-law-like scenarios. Assuming v(e): v(mu): v(tau) = 1:1:1, and an equal flux of neutrinos and antineutrinos, we find that the astrophysical neutrino spectrum is compatible with an unbroken power law, with a preferred spectral index of 2.87(-0.19)(+0.20) for the 68% confidence interval