Immunization is a cornerstone of public health policy and is demonstrably highly cost-effective when used to protect child health. Although it could be argued that immunology has not thus far ...contributed much to vaccine development, in that most of the vaccines we use today were developed and tested empirically, it is clear that there are major challenges ahead to develop new vaccines for difficult-to-target pathogens, for which we urgently need a better understanding of protective immunity. Moreover, recognition of the huge potential and challenges for vaccines to control disease outbreaks and protect the older population, together with the availability of an array of new technologies, make it the perfect time for immunologists to be involved in designing the next generation of powerful immunogens. This Review provides an introductory overview of vaccines, immunization and related issues and thereby aims to inform a broad scientific audience about the underlying immunological concepts.
The COVID-19 pandemic is unlikely to end until there is global roll-out of vaccines that protect against severe disease and preferably drive herd immunity. Regulators in numerous countries have ...authorised or approved COVID-19 vaccines for human use, with more expected to be licensed in 2021. Yet having licensed vaccines is not enough to achieve global control of COVID-19: they also need to be produced at scale, priced affordably, allocated globally so that they are available where needed, and widely deployed in local communities. In this Health Policy paper, we review potential challenges to success in each of these dimensions and discuss policy implications. To guide our review, we developed a dashboard to highlight key characteristics of 26 leading vaccine candidates, including efficacy levels, dosing regimens, storage requirements, prices, production capacities in 2021, and stocks reserved for low-income and middle-income countries. We use a traffic-light system to signal the potential contributions of each candidate to achieving global vaccine immunity, highlighting important trade-offs that policy makers need to consider when developing and implementing vaccination programmes. Although specific datapoints are subject to change as the pandemic response progresses, the dashboard will continue to provide a useful lens through which to analyse the key issues affecting the use of COVID-19 vaccines. We also present original data from a 32-country survey (n=26 758) on potential acceptance of COVID-19 vaccines, conducted from October to December, 2020. Vaccine acceptance was highest in Vietnam (98%), India (91%), China (91%), Denmark (87%), and South Korea (87%), and lowest in Serbia (38%), Croatia (41%), France (44%), Lebanon (44%), and Paraguay (51%).
Tip-enhanced Raman spectroscopy (TERS) is a powerful tool for non-destructive and label-free surface molecular mapping at the nanoscale. However, to date nanoscale resolution chemical imaging in a ...liquid environment has not been possible, in part due to the lack of robust TERS probes that are stable when immersed in a liquid. In this work, we have addressed this challenge by developing plasmonically-active TERS probes with a multilayer metal coating structure that can be successfully used within a liquid environment. Using these novel TERS probes, we have compared the plasmonic enhancement of TERS signals in air and water environments for both gap mode and non-gap mode configurations and show that in both cases the plasmonic enhancement decreases in water. To better understand the signal attenuation in water, we have performed numerical simulations that revealed a negative correlation between the electric field enhancement at the TERS probe-apex and the refractive index of the surrounding medium. Finally, using these robust probes we demonstrate TERS imaging with nanoscale spatial resolution in a water environment for the first time by employing single-wall carbon nanotubes as a model sample. Our findings are expected to broaden the scope of TERS to a range of scientific disciplines in which nanostructured solid-liquid interfaces play a key role.
The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 1 million deaths in the first 6 months of the pandemic and huge economic and social upheaval ...internationally. An efficacious vaccine is essential to prevent further morbidity and mortality. Although some countries might deploy COVID-19 vaccines on the strength of safety and immunogenicity data alone, the goal of vaccine development is to gain direct evidence of vaccine efficacy in protecting humans against SARS-CoV-2 infection and COVID-19 so that manufacture of efficacious vaccines can be selectively upscaled. A candidate vaccine against SARS-CoV-2 might act against infection, disease, or transmission, and a vaccine capable of reducing any of these elements could contribute to disease control. However, the most important efficacy endpoint, protection against severe disease and death, is difficult to assess in phase 3 clinical trials. In this Review, we explore the challenges in assessing the efficacy of candidate SARS-CoV-2 vaccines, discuss the caveats needed to interpret reported efficacy endpoints, and provide insight into answering the seemingly simple question, “Does this COVID-19 vaccine work?”
Our aim was to estimate provisional willingness to receive a coronavirus 2019 (COVID-19) vaccine, identify predictive socio-demographic factors, and, principally, determine potential causes in order ...to guide information provision.
A non-probability online survey was conducted (24th September-17th October 2020) with 5,114 UK adults, quota sampled to match the population for age, gender, ethnicity, income, and region. The Oxford COVID-19 vaccine hesitancy scale assessed intent to take an approved vaccine. Structural equation modelling estimated explanatory factor relationships.
71.7% (
=3,667) were willing to be vaccinated, 16.6% (
=849) were very unsure, and 11.7% (
=598) were strongly hesitant. An excellent model fit (RMSEA=0.05/CFI=0.97/TLI=0.97), explaining 86% of variance in hesitancy, was provided by beliefs about the collective importance, efficacy, side-effects, and speed of development of a COVID-19 vaccine. A second model, with reasonable fit (RMSEA=0.03/CFI=0.93/TLI=0.92), explaining 32% of variance, highlighted two higher-order explanatory factors: 'excessive mistrust' (
=0.51), including conspiracy beliefs, negative views of doctors, and need for chaos, and 'positive healthcare experiences' (
=-0.48), including supportive doctor interactions and good NHS care. Hesitancy was associated with younger age, female gender, lower income, and ethnicity, but socio-demographic information explained little variance (9.8%). Hesitancy was associated with lower adherence to social distancing guidelines.
COVID-19 vaccine hesitancy is relatively evenly spread across the population. Willingness to take a vaccine is closely bound to recognition of the collective importance. Vaccine public information that highlights prosocial benefits may be especially effective. Factors such as conspiracy beliefs that foster mistrust and erode social cohesion will lower vaccine up-take.
Summary
The significantly higher mortality rates seen in the elderly compared with young children during the coronavirus disease 2019 (Covid‐19) pandemic is likely to be driven in part by an impaired ...immune response in older individuals. Cytomegalovirus (CMV) seroprevalence approaches 80% in the elderly. CMV has been shown to accelerate immune ageing by affecting peripheral blood T cell phenotypes and increasing inflammatory mediated cytokines such as IL‐6. The elderly with pre‐existing but clinically silent CMV infection may therefore be particularly susceptible to severe Covid‐19 disease and succumb to a cytokine storm which may have been promoted by CMV. Here, we evaluate the potential role of CMV in those with severe Covid‐19 disease and consider how this relationship can be investigated in current research studies.
The temporal and spatial change in trends of antimicrobial resistance (AMR) in typhoid have not been systematically studied, and such information will be critical for defining intervention, as well ...as planning sustainable prevention strategies.
To identify the phenotypic trends in AMR, 13,833 individual S. Typhi isolates, reported from 1973 to 2018 in 62 publications, were analysed to determine the AMR preponderance over time. Separate analyses of molecular resistance determinants present in over 4,000 isolates reported in 61 publications were also conducted. Multi-drug resistant (MDR) typhoid is in decline in Asia in a setting of high fluoroquinolone resistance while it is on the increase in Africa. Mutations in QRDRs in gyrA (S83F, D87N) and parC (S80I) are the most common mechanisms responsible for fluoroquinolone resistance. Cephalosporin resistant S. Typhi, dubbed extensively drug-resistant (XDR) is a real threat and underscores the urgency in deploying the Vi-conjugate vaccines.
From these observations, it appears that AMR in S. Typhi will continue to emerge leading to treatment failure, changes in antimicrobial policy and further resistance developing in S. Typhi isolates and other Gram-negative bacteria in endemic regions. The deployment of typhoid conjugate vaccines to control the disease in endemic regions may be the best defence.
Confocal and surface-enhanced Raman spectroscopy (SERS) are powerful techniques for molecular characterization; however, they suffer from the drawback of diffraction-limited spatial resolution. ...Tip-enhanced Raman spectroscopy (TERS) overcomes this limitation and provides chemical information at length scales in the tens of nanometers. In contrast to alternative approaches to nanoscale chemical analysis, TERS is label free, is non-destructive, and can be performed in both air and liquid environments, allowing its use in a diverse range of applications. Atomic force microscopy (AFM)-based TERS is especially versatile, as it can be applied to a broad range of samples on various substrates. Despite its advantages, widespread uptake of this technique for nanoscale chemical imaging has been inhibited by various experimental challenges, such as limited lifetime, and the low stability and yield of TERS probes. This protocol details procedures that will enable researchers to reliably perform TERS imaging using a transmission-mode AFM-TERS configuration on both biological and non-biological samples. The procedure consists of four stages: (i) preparation of plasmonically active TERS probes; (ii) alignment of the TERS system; (iii) experimental procedures for nanoscale imaging using TERS; and (iv) TERS data processing. We provide procedures and example data for a range of different sample types, including polymer thin films, self-assembled monolayers (SAMs) of organic molecules, photocatalyst surfaces, small molecules within biological cells, single-layer graphene and single-walled carbon nanotubes in both air and water. With this protocol, TERS probes can be prepared within ~23 h, and each subsequent TERS experimental procedure requires 3-5 h.
Non-specific effects (NSE) or heterologous effects of vaccines are proposed to explain observations in some studies that certain vaccines have an impact beyond the direct protection against infection ...with the specific pathogen for which the vaccines were designed. The importance and implications of such effects remain controversial. There are several known immunological mechanisms which could lead to NSE, since it is widely recognised that the generation of specific immunity is initiated by non-specific innate immune mechanisms that may also have wider effects on adaptive immune function. However, there are no published studies that demonstrate a mechanistic link between such immunological phenomena and clinically relevant NSE in humans. While it is highly plausible that some vaccines do have NSE, their magnitude and duration, and thus importance, remain uncertain. Although the WHO recently concluded that current evidence does not justify changes to immunisation policy, further studies of sufficient size and quality are needed to assess the importance of NSE for all-cause mortality. This could provide insights into vaccine immunobiology with important implications for infant health and survival.
The mechanism by which Cu catalyst pretreatments control graphene nucleation density in scalable chemical vapor deposition (CVD) is systematically explored. The intrinsic and extrinsic carbon ...contamination in the Cu foil is identified by time-of-flight secondary ion mass spectrometry as a major factor influencing graphene nucleation and growth. By selectively oxidizing the backside of the Cu foil prior to graphene growth, a drastic reduction of the graphene nucleation density by 6 orders of magnitude can be obtained. This approach decouples surface roughness effects and at the same time allows us to trace the scavenging effect of oxygen on deleterious carbon impurities as it permeates through the Cu bulk. Parallels to well-known processes in Cu metallurgy are discussed. We also put into context the relative effectiveness and underlying mechanisms of the most widely used Cu pretreatments, including wet etching and electropolishing, allowing a rationalization of current literature and determination of the relevant parameter space for graphene growth. Taking into account the wider CVD growth parameter space, guidelines are discussed for high-throughput manufacturing of “electronic-quality” monolayer graphene films with domain size exceeding 1 mm, suitable for emerging industrial applications, such as electronics and photonics.
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