Although virus-like particle (VLP) vaccines were shown to be effective against several viruses, their advantage over vaccines that include envelope protein only is not completely clear, particularly for mRNA-encoded VLPs. We conducted a side-by-side comparison of the immunogenicity and protective efficacy of mRNA vaccines encoding the Marburg virus (MARV) full-length glycoprotein (GP) delivered alone or as a VLP. Electron microscopy confirmed VLP formation when MARV GP and matrix protein VP40 were coexpressed. We vaccinated guinea pigs with a 2-component mRNA vaccine encoding GP and VP40 (VLP) or GP alone. At the highest dose, both vaccines protected fully, although the VLP vaccine elicited a slightly lower humoral response than did the GP-only mRNA vaccine. However, at low doses, GP-only mRNA conferred 100% protection, whereas the VLP vaccine conferred only partial protection. In mice, VLP mRNA induced a moderate preference for GP-specific CD8+ T cell responses, whereas the GP-only mRNA somewhat favored CD4+ T cell responses. Guinea pig whole-blood RNA-Seq revealed that the VLP vaccine downregulated genes associated with various biological and metabolic processes, including the NF-κB signaling pathway, whereas the GP-only vaccine upregulated IFN signaling. Overall, the VLP mRNA vaccine was less immunogenic and protective, whereas the GP-only mRNA vaccine conferred robust protection with a dose of as little as 1 μg in guinea pigs.
Respiratory tract vaccination has an advantage of needle-free delivery and induction of mucosal immune response in the portal of SARS-CoV-2 entry. We utilized human parainfluenza virus type 3 vector to generate constructs expressing the full spike (S) protein of SARS-CoV-2, its S1 subunit, or the receptor-binding domain, and tested them in hamsters as single-dose intranasal vaccines. The construct bearing full-length S induced high titers of neutralizing antibodies specific to S protein domains critical to the protein functions. Robust memory T cell responses in the lungs were also induced, which represent an additional barrier to infection and should be less sensitive than the antibody responses to mutations present in SARS-CoV-2 variants. Following SARS-CoV-2 challenge, animals were protected from the disease and detectable viral replication. Vaccination prevented induction of gene pathways associated with inflammation. These results indicate advantages of respiratory vaccination against COVID-19 and inform the design of mucosal SARS-CoV-2 vaccines.
Background: Successful containment strategies for SARS-CoV-2, the causative virus of the COVID-19 pandemic, have involved widespread population testing that identifies infections early and enables rapid contact tracing. In this study, we developed a rapid and inexpensive RT-qPCR testing pipeline for population-level SARS-CoV-2 detection, and used this pipeline to establish a clinical laboratory dedicated to COVID-19 testing at the University of California San Diego (UCSD) with a processing capacity of 6,000 samples per day and next-day result turnaround times. Methods and findings: Using this pipeline, we screened 6,786 healthcare workers and first responders, and 21,220 students, faculty, and staff from UCSD. Additionally, we screened 6,031 preschool-grade 12 students and staff from public and private schools across San Diego County that remained fully or partially open for in-person teaching during the pandemic. Between April 17, 2020 and February 5, 2021, participants provided 161,582 nasal swabs that were tested for the presence of SARS-CoV-2. Overall, 752 positive tests were obtained, yielding a test positivity rate of 0.47%. While the presence of symptoms was significantly correlated with higher viral load, most of the COVID-19 positive participants who participated in symptom surveys were asymptomatic at the time of testing. The positivity rate among preschool-grade 12 schools that remained open for in-person teaching was similar to the positivity rate at UCSD and lower than that of San Diego County, with the children in private schools being less likely to test positive than the adults at these schools. Conclusions: Most schools across the United States have been closed for in-person learning for much of the 2020-2021 school year, and their safe reopening is a national priority. However, as there are no vaccines against SARS-CoV-2 currently available to the majority of school-aged children, the traditional strategies of mandatory masking, physical distancing, and repeated viral testing of students and staff remain key components of risk mitigation in these settings. The data presented here suggest that the safety measures and repeated testing actions taken by participating healthcare and educational facilities were effective in preventing outbreaks, and that a similar combination of risk-mitigation strategies and repeated testing may be successfully adopted by other healthcare and educational systems.
In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.
The CLIA status of a lab that generates research data is regularly perceived to interfere with the ability of individuals to access data about themselves for a variety of reasons, including to advance research as an active participant who seeks to contribute to the research process in ways that go beyond serving solely as a source of tissue or data for others to use. Barbara Evans and Susan Wolf have made a compelling case that, contrary to conventional wisdom, the Clinical Laboratory Improvement Amendments of 1988 (CLIA) do not prohibit the return of research results from a non-CLIA lab when that return is done for any reason other than “for the purpose of providing information for the diagnosis, prevention, or treatment of any disease or impairment of, or the assessment of the health of, human beings. As a result of this analysis, two pearls of conventional wisdom that have impeded efforts to engage, respect, and honor the civil rights of research participants logically fall.
Der demografische Wandel lasst den Druck auf die Unternehmen steigen, sich zukunftig starker als bisher fur die Gesundheit ihrer Mitarbeiter einzusetzen. Auch kann ein gesundheitsforderliches Engagement einen Konkurrenzvorteil gegenuber Mitbewerbern bedeuten, um so die dringend benotigten Fachkrafte finden, langfristig an sich binden und arbeitsfahig halten zu konnen. Das Betriebliche Gesundheitsmanagement stellt dabei einen zentralen Baustein dar: Rahmenbedingungen, Strukturen und Prozesse sind in den Betrieben dahingehend zu entwickeln und umzusetzen, dass sowohl die Verhaltnisse im Betrieb gesundheitsgerecht und gesundheitsfordernd gestaltet wie auch die Beschaftigten in den Betrieben zu einem gesundheitsfordernden Verhalten befahigt werden. Masnahmen des Betrieblichen Gesundheitsmanagement s sollten daher fur die Unternehmensfuhrungen mehr sein als nur eine Public-Relation-Masnahme fur die eigene Belegschaft, denn nur durch gesunde und motivierte Beschaftige wird ein Unternehmen auch in Zukunft innovations- und wettbewerbsfahig sein und bleiben konnen. Nicht jede gesundheitsforderliche Masnahme bringt dabei zwangslaufig den erhofften Erfolg, insbesondere, wenn Interventionen nach dem »Gieskannenprinzip« fur alle Beschaftigten unreflektiert angewendet werden. Die Handlungsstrategien in der Betrieblichen Gesundheitsforderung sind bisher vor allem in Grosbetrieben entwickelt worden und fusen auf den dortigen Erfahrungen und deren spezifischem Bedarf. Doch sind diese Ergebnisse auf jede andere Zielgruppe ubertragbar? Der diesjahrige Fehlzeiten-Report legt den Fokus auf die schwer erreichbaren Zielgruppen und fragt nach passenden innovativen Strategien fur das Betriebliche Gesundheitsmanagement.
A Facebook study that manipulated news feeds was not definitively unethical and offered valuable insight into social behaviour, says Michelle Meyer.
Recently, both legal scholars and lawmakers have called for evidence-based practice (EBP) across a variety of “practice” areas, including not only clinical medicine, health care delivery and public health practice, but also legal services, education, criminal justice, housing, environmental regulation and many other areas of law- and policy- making. Drawing on the most longstanding version of EBP — evidence-based medicine (EBM) — they reasonably argue that decisions affecting human welfare should be based on sound evidence about the comparative effects of alternatives. Rigorously studying the effects of an innovative practice on a small scale before implementing it more widely limits the extent of any negative impact it might have. And retrospective testing of already-accepted practices can identify ineffective and inefficient practices.