SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness

A vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to control the coronavirus disease 2019 (COVID-19) global pandemic. Structural studies have led to the development of mutations that stabilize Betacoronavirus spike proteins in the prefusion state, improving their expression and increasing immunogenicity1. This principle has been applied to design mRNA-1273, an mRNA vaccine that encodes a SARS-CoV-2 spike protein that is stabilized in the prefusion conformation. Here we show that mRNA-1273 induces potent neutralizing antibody responses to both wild-type (D614) and D614G mutant2 SARS-CoV-2 as well as CD8+ T cell responses, and protects against SARS-CoV-2 infection in the lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a phase III trial to evaluate its efficacy

Integrated community case management in a peri-urban setting: a qualitative evaluation in Wakiso District, Uganda.

Integrated community case management (iCCM) strategies aim to reach poor communities by providing timely access to treatment for malaria, pneumonia and diarrhoea for children under 5 years of age. Community health workers, known as Village Health Teams (VHTs) in Uganda, have been shown to be effective in hard-to-reach, underserved areas, but there is little evidence to support iCCM as an appropriate strategy in non-rural contexts. This study aimed to inform future iCCM implementation by exploring caregiver and VHT member perceptions of the value and effectiveness of iCCM in peri-urban settings in Uganda.A qualitative evaluation was conducted in seven villages in Wakiso district, a rapidly urbanising area in central Uganda. Villages were purposively selected, spanning a range of peri-urban settlements experiencing rapid population change. In each village, rapid appraisal activities were undertaken separately with purposively selected caregivers (n = 85) and all iCCM-trained VHT members (n = 14), providing platforms for group discussions. Fifteen key informant interviews were also conducted with community leaders and VHT members. Thematic analysis was based on the 'Health Access Livelihoods Framework'.iCCM was perceived to facilitate timely treatment access and improve child health in peri-urban settings, often supplanting private clinics and traditional healers as first point of care. Relative to other health service providers, caregivers valued VHTs' free, proximal services, caring attitudes, perceived treatment quality, perceived competency and protocol use, and follow-up and referral services. VHT effectiveness was perceived to be restricted by inadequate diagnostics, limited newborn care, drug stockouts and VHT member absence - factors which drove utilisation of alternative providers. Low community engagement in VHT selection, lack of referral transport and poor availability of referral services also diminished perceived effectiveness. The iCCM strategy was widely perceived to result in economic savings and other livelihood benefits.In peri-urban areas, iCCM was perceived as an effective, well-utilised strategy, reflecting both VHT attributes and gaps in existing health services. Depending on health system resources and organisation, iCCM may be a useful transitional service delivery approach. Implementation in peri-urban areas should consider tailored community engagement strategies, adapted selection criteria, and assessment of population density to ensure sufficient coverage

Using the Living CV to help students take ownership of their learning gain

There is an increasing emphasis on embedding employability skills and experience within the higher education curriculum to address new concepts of ‘learning gain’ and the perceived student demand for a value for money experience. An exploratory study, at a southern university in the UK, found that students articulated an improved work readiness when they were presented the ‘Living CV’, an initiative that connects programme learning outcomes into CV outputs. During 2018, a larger, mixed methods study (n=127) was conducted across all three years of fashion degrees. Students completed a pre and post questionnaire before and after a presentation on the Living CV and their views were further explored in a focus group and interviews. Results found that the Living CV presentation heightened students’ awareness of the applicability of their programme learning to their future employability and how they could use their academic learning outcomes on their CV as a tool to achieve this. The study recommends that personalised and explicit coaching on ‘work literacy’ should be integrated into university programmes at all levels to include the Living CV, discussion about and experience in the world of work, increased employer engagement and preparation for interview

Pilot-scale adenovirus seed production through concurrent virus release and concentration by hollow fiber filtration

Recovery of recombinant adenoviruses from infected mammalian cell cultures often requires multiple unit operations such as cell lysis for virus release, microfiltration for clarification, and ultrafiltration for concentration. While development of these multiple unit operations is relatively straightforward, implementation under aseptic conditions in a closed system can be challenging for the production of virus seed at industrial scales. In this study, we have developed a simple, single-step, scaleable process to effectively recover adenoviruses from infected PER.C6 cell cultures for the production of concentrated adenovirus seeds under aseptic conditions. Specifically, hollow fiber tangential flow filtration technology was applied to maximize cell lysis of infected cultures for virus release while simultaneously concentrating the virus to an appropriate level of volume reduction. Hollow fiber filters with small lumen diameter of 0.5 mm were chosen to maximize the wall shear for a highly effective cell lysis and virus release. Cell lysis and virus release were shown to correlate with the exposure time in the hollow fiber cartridge: the shear zone. In most cases, a virus recovery yield of more than 80% and a 15- to 20-fold concentration (or up to 95% volume reduction) was achieved in less than 2 h of processing time. The virus seeds prepared using this process at lab scale and at 300-L scale without clarification have been successfully tested for sterility and potency and used for subsequent infection with consistent virus productivity. This process should enable rapid production of adenovirus seeds with minimal unit operations and high efficiency recovery for adenovirus production at 1000-L scale

The Role of Strategic Emotional Intelligence in Predicting Adolescents’ Academic Achievement: Possible Interplays with Verbal Intelligence and Personality

As recent meta-analyses confirmed that emotional intelligence (EI), particularly strategic EI, adjoins intelligence and personality in predicting academic achievement, we explored possible arrangements in which these predictors affect the given outcome in adolescents. Three models, with versions including either overall strategic EI or its branches, were considered: (a) a mediation model, whereby strategic EI partially mediates the effects of verbal intelligence (VI) and personality on achievement; the branch-level version assumed that emotion understanding affects achievement in a cascade via emotion management; (b) a direct effects model, with strategic EI/branches placed alongside VI and personality as another independent predictor of achievement; and (c) a moderation model, whereby personality moderates the effects of VI and strategic EI/branches on achievement. We tested these models in a sample of 227 students (M = 16.50 years) and found that both the mediation and the direct effects model with overall strategic EI fit the data; there was no support for a cascade within strategic EI, nor for the assumption that personality merely moderates the effects of abilities on achievement. Principally, strategic EI both mediated the effects of VI and openness, and independently predicted academic achievement, and it did so through emotion understanding directly, “skipping” emotion management