Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses.

BACKGROUND: The COVID-19 pandemic continues to cause morbidity and mortality worldwide. Most approved COVID-19 vaccines generate a neutralizing antibody response that primarily targets the highly variable receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. SARS-CoV-2 "variants of concern" have acquired mutations in this domain allowing them to evade vaccine-induced humoral immunity. Recent approaches to improve the breadth of protection beyond SARS-CoV-2 have required the use of mixtures of RBD antigens from different sarbecoviruses. It may therefore be beneficial to develop a vaccine in which the protective immune response targets a more conserved region of the S protein. METHODS: Here we have developed a vaccine based on the conserved S2 subunit of the S protein and optimized the adjuvant and immunization regimen in Syrian hamsters and BALB/c mice. We have characterized the efficacy of the vaccine against SARS-CoV-2 variants and other coronaviruses. FINDINGS: Immunization with S2-based constructs elicited a broadly cross-reactive IgG antibody response that recognized the spike proteins of not only SARS-CoV-2 variants, but also SARS-CoV-1, and the four endemic human coronaviruses. Importantly, immunization reduced virus titers in respiratory tissues in vaccinated animals challenged with SARS-CoV-2 variants B.1.351 (beta), B.1.617.2 (delta), and BA.1 (omicron) as well as a pangolin coronavirus. INTERPRETATION: These results suggest that S2-based constructs can elicit a broadly cross-reactive antibody response resulting in limited virus replication, thus providing a framework for designing vaccines that elicit broad protection against coronaviruses. FUNDING: NIH, Japan Agency for Medical Research and Development, Garry Betty/ V Foundation Chair Fund, and NSF.

Development of Ethical COVID-19 Antibody Testing that Adheres to Pro-Life Principles

The use of cell lines derived from elective abortions in the development and production of COVID vaccines was opposed by the Catholic church who encouraged pharmaceutical companies and governmental health agencies to produce and distribute ethical vaccines that do not create problems of conscience for healthcare providers or those requiring vaccination. In response to the church?s call for ethical alternatives in research and development of COVID vaccines, we present an approach for the measurement of Anti?SARS-CoV-2 Ig antibodies in blood plasma (COVID-19 Antibody test) that does not utilize any products produced in aborted fetal cell lines. The SARS-CoV-2 RBD protein used in this test was produced in Chinese Hamster Ovary (CHO) cells and test performance for determination of SARS-CoV-2 seroconversion was equivalent to a commercially available COVID-19 antibody test that utilized RBD protein and other reagents produced in embryonic cell lines.

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission.

Understanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.

Attaining a British consensus statement on managing idiopathic congenital talipes equinovarus (CTEV) through a Delphi process: a study protocol.

INTRODUCTION: Idiopathic congenital talipes equinovarus (CTEV) is the most common congenital limb deformity. Non-operative intervention using the Ponseti method has shown to be superior to soft tissue release and has become the gold standard for first-line treatment. However, numerous deviations from the Ponseti protocol are still reported following incomplete correction or deformity relapse. Significant variation in treatment protocols and management is evident in the literature. Reducing geographical treatment variation has been identified as one of The James Lind Alliance priorities in children's orthopaedics. For this reason, the British Society of Children's Orthopaedic Surgery (BSCOS) commissioned a consensus document to form a benchmark for practitioners and ensure consistent high quality care for children with CTEV. METHODS AND ANALYSIS: The consensus will follow an established Delphi approach aiming at gaining an agreement on the items to be included in the consensus statement for the management of primary idiopathic CTEV up to walking age. The process will include the following steps: (1) establishing a steering group, (2) steering group meetings, (3) a two-round Delphi survey aimed at BSCOS members, (4) final consensus meeting and (5) dissemination of the consensus statement. Degree of agreement for each item will be predetermined. Descriptive statistics will be used for analysis of the Delphi survey results. ETHICS AND DISSEMINATION: No patient involvement is required for this project. Informed consent will be assumed from participants taking part in the Delphi survey. Study findings will be published in an open access journal and presented at relevant national and international conferences. Charities and associations will be engaged to promote awareness of the consensus statement.

The Impact of COVID-19 Restrictions on Victim Advocacy Agency Utilization Across Pennsylvania.

This brief report highlights the impact of the COVID-19 restrictions on the utilization of Victim Advocacy Agencies' (VAAs') services across Pennsylvania, using VAA utilization data from 2019-2020. VAA utilization data in this report were collected from 2019-2020 by the Pennsylvania Coalition Against Rape (PCAR). VAA utilization data were anchored to COVID-19 restriction timelines, defined by the Pennsylvania Office of the Governor. For each month, a percent change in VAA utilization (e.g., Jan 2020 utilization compared to Jan 2019 utilization) was calculated. A one-way ANOVA was run to assess whether the association between restriction phase and percent change in overall VAA utilization from 2019 to 2020 was statistically significant. A substantial decrease in VAA utilization was observed once lockdown restrictions were enacted, as well as a sustained decrease in utilization between 2019 and 2020. When restrictions were eased, an increase in service utilization was noted. This pattern of findings held for the three variables assessed: hotline utilization, new client, and medical accompaniments for FREs per month. The one-way ANOVA confirmed a statistically significant decrease in overall VAA utilization when comparing the most severe COVID-19 related restrictions to both pre-COVID and less severe restrictions. A variety of barriers (e.g., financial instability, loss of childcare, technology access, chronic physical proximity to abuser, hospital visitation restrictions, fears of contracting the virus) may result in decreased utilization of VAA services. Future research should investigate the relevance of potential causal mechanisms behind VAA utilization to help inform intervention approaches.

TIME REMEMBERED

Omnia regit tempus This is the fundamental law of the comedia nueva, in Marc Vitse's enduring formulation of dramaturgy (275).1 It took on new significance in 2020, a year which the global pandemic that is still raging in too many parts of the world changed our shared sense of time, whether lived as uninterrupted days of home confinement or of frontline work. For most, its capricious new rules began just before or right after the World Health Organization declared COVID-19 a pandemic on 11 March 2020. Brown notes as well that though such lowcut bodices were prohibited in 1639 by royal decree, the informal nature of the painting and the likelihood that the anonymous sitter was part of the painter's household make it plausible that she wore this costume in casual defiance of the sumptuary law (118).

Multivalent nanoparticle-based vaccines protect hamsters against SARS-CoV-2 after a single immunization.

The COVID-19 pandemic continues to wreak havoc as worldwide SARS-CoV-2 infection, hospitalization, and death rates climb unabated. Effective vaccines remain the most promising approach to counter SARS-CoV-2. Yet, while promising results are emerging from COVID-19 vaccine trials, the need for multiple doses and the challenges associated with the widespread distribution and administration of vaccines remain concerns. Here, we engineered the coat protein of the MS2 bacteriophage and generated nanoparticles displaying multiple copies of the SARS-CoV-2 spike (S) protein. The use of these nanoparticles as vaccines generated high neutralizing antibody titers and protected Syrian hamsters from a challenge with SARS-CoV-2 after a single immunization with no infectious virus detected in the lungs. This nanoparticle-based vaccine platform thus provides protection after a single immunization and may be broadly applicable for protecting against SARS-CoV-2 and future pathogens with pandemic potential.