Nature communications
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Nature communications · Jan 2021
Psychological characteristics associated with COVID-19 vaccine hesitancy and resistance in Ireland and the United Kingdom.
Identifying and understanding COVID-19 vaccine hesitancy within distinct populations may aid future public health messaging. Using nationally representative data from the general adult populations of Ireland (N = 1041) and the United Kingdom (UK; N = 2025), we found that vaccine hesitancy/resistance was evident for 35% and 31% of these populations respectively. ⋯ In both populations, those resistant to a COVID-19 vaccine were less likely to obtain information about the pandemic from traditional and authoritative sources and had similar levels of mistrust in these sources compared to vaccine accepting respondents. Given the geographical proximity and socio-economic similarity of the populations studied, it is not possible to generalize findings to other populations, however, the methodology employed here may be useful to those wishing to understand COVID-19 vaccine hesitancy elsewhere.
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Nature communications · Dec 2020
A single dose of recombinant VSV-∆G-spike vaccine provides protection against SARS-CoV-2 challenge.
The COVID-19 pandemic caused by SARS-CoV-2 imposes an urgent need for rapid development of an efficient and cost-effective vaccine, suitable for mass immunization. Here, we show the development of a replication competent recombinant VSV-∆G-spike vaccine, in which the glycoprotein of VSV is replaced by the spike protein of SARS-CoV-2. In-vitro characterization of this vaccine indicates the expression and presentation of the spike protein on the viral membrane with antigenic similarity to SARS-CoV-2. ⋯ We show that a single-dose vaccination results in a rapid and potent induction of SARS-CoV-2 neutralizing antibodies. Importantly, vaccination protects hamsters against SARS-CoV-2 challenge, as demonstrated by the abrogation of body weight loss, and alleviation of the extensive tissue damage and viral loads in lungs and nasal turbinates. Taken together, we suggest the recombinant VSV-∆G-spike as a safe, efficacious and protective vaccine against SARS-CoV-2.
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Nature communications · Dec 2020
Deep learning-based cross-classifications reveal conserved spatial behaviors within tumor histological images.
Histopathological images are a rich but incompletely explored data type for studying cancer. Manual inspection is time consuming, making it challenging to use for image data mining. Here we show that convolutional neural networks (CNNs) can be systematically applied across cancer types, enabling comparisons to reveal shared spatial behaviors. ⋯ Patterns for TP53 mutations can also be detected, with WSI self- and cross-tissue AUCs ranging from 0.65-0.80. Finally, we comparatively evaluate CNNs on 170 breast and colon cancer images with pathologist-annotated nuclei, finding that both cellular and intercellular regions contribute to CNN accuracy. These results demonstrate the power of CNNs not only for histopathological classification, but also for cross-comparisons to reveal conserved spatial behaviors across tumors.
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Nature communications · Dec 2020
Functionally impaired plasmacytoid dendritic cells and non-haematopoietic sources of type I interferon characterize human autoimmunity.
Autoimmune connective tissue diseases arise in a stepwise fashion from asymptomatic preclinical autoimmunity. Type I interferons have a crucial role in the progression to established autoimmune diseases. The cellular source and regulation in disease initiation of these cytokines is not clear, but plasmacytoid dendritic cells have been thought to contribute to excessive type I interferon production. ⋯ In addition, plasmacytoid dendritic cells have a transcriptional signature indicative of cellular stress and senescence accompanied by increased telomere erosion. In preclinical autoimmunity, we show a marked enrichment of an interferon signature in the skin without infiltrating immune cells, but with interferon-κ production by keratinocytes. In conclusion, non-hematopoietic cellular sources, rather than plasmacytoid dendritic cells, are responsible for interferon production prior to clinical autoimmunity.
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Nature communications · Nov 2020
Development of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform.
Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We demonstrate the construction of a vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. ⋯ We show that mice immunized with these sMVA vectors develop robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.