86 research outputs found
Evaluation of a multiplexed immunoassay for assessing long-term humoral immunity Orthopoxviruses
No full textCRediT authorship contribution statement Bethany Hicks: Writing – review & editing, Writing – original draft, Methodology, Investigation, Formal analysis, Conceptualization. Scott Jones: Writing – review & editing, Supervision, Methodology, Investigation, Conceptualization. Helen Callaby: Writing – review & editing. Daniel Bailey: Writing – review & editing. Claire Gordon: Writing – review & editing. Tommy Rampling: Writing – review & editing. Catherine Houlihan: Writing – review & editing. Ezra Linley: Writing – review & editing. Simon Tonge: Writing – review & editing. Clarissa Oeser: Writing – review & editing. Rachael Jones: Writing – review & editing. Marcus Pond: Writing – review & editing. Ravi Mehta: Writing – review & editing. Deborah Wright: Writing – review & editing. Bassam Hallis: Writing – review & editing, Funding acquisition. Cathy Rowe: Writing – review & editing, Funding acquisition. Ashley Otter: Writing – review & editing, Supervision, Methodology, Funding acquisition, Conceptualization.Peer reviewe
Emerg Infect Dis
No full textRecent years have seen unprecedented investment in research and development for countermeasures for high-threat pathogens, including specific and ambitious objectives for development of diagnostics, therapeutics, and vaccines. The inadequate availability of biological reference materials for these pathogens poses a genuine obstacle in pursuit of these objectives, and the lack of a comprehensive and equitable framework for developing reference materials is a weakness. We outline the need for internationally standardized biological materials for high-threat pathogens as a core element of global health security. We also outline the key components of a framework for addressing this deficiency
International biological reference preparations for emerging infectious diseases: vital tools in epidemic preparedness
No full textPoster 1506
International Biological Reference Preparations for Epidemic Infectious Diseases
No full textRecent years have seen unprecedented investment in research and development for countermeasures for high-threat pathogens, including specific and ambitious objectives for development of diagnostics, therapeutics, and vaccines. The inadequate availability of biological reference materials for these pathogens poses a genuine obstacle in pursuit of these objectives, and the lack of a comprehensive and equitable framework for developing reference materials is a weakness. We outline the need for internationally standardized biological materials for high-threat pathogens as a core element of global health security. We also outline the key components of a framework for addressing this deficiency
Chymical Collections: Seventeenth Century textual transmutations in the work of Arthur Dee
No full textThis dissertation is a biography of a text, Fasciculus Chemicus (1631). The seventeenth-century life of this text, from its inception to its vernacularization, sheds light on broader natural philosophical and textual issues inherent to alchemical knowledge-making. The first chapter of this case-study is a survey of all available biographical information of its author, Arthur Dee, supplemented and contextualized with original primary source discoveries. This provides a setting for the creation of Fasciculus Chemicus as well as juxtaposes political issues of authority, patronage, and medical practice of a seventeenth-century courtly physician. The second chapter addresses the hand-press production and subsequent intentional anomalies found in the printed Fasciculus Chemicus, of which there are two editions (1631, 1650). Then, a bibliographical description and analysis is provided for the three issues of the first edition, which leads into investigations of ghost editions and a special dedicatory Rosicrucian issue. The third chapter examines the possibility of an alchemical scribal culture through the lens of scribal copies of Fasciculus Chemicus and other seventeenth-century alchemical manuscripts copies from print. This presents the reciprocal nature of material reuse and recycling between manuscript and hand-press texts. The fourth chapter deals with material evidence of alchemical speculation in the margins of seventeenth-century alchemical texts such as drawings and doodles, creative cross-referencing, and ciphers and pseudonomia. The epilogue to the story of the seventeenth-century life of Fasciculus Chemicus responds to issues of English vernacularization and curation of knowledge through the scope of ‘chymical collections’ such as Theatrum Chemicum (1602-1661) and Theatrum Chemicum Britannicum (1652). This allows for broader questions to be posed regarding Baroque science and alchemical knowledge-making practices
Imported malaria: key messages in an era of elimination.
No full textDespite concerted efforts to eliminate malaria, it remains a major global cause of morbidity and mortality with over 200 million annual cases. Significant gains have been made, with the annual global malaria incidence and mortality halving over the past twenty years, using tools such as long-lasting insecticide-treated bed nets and artemisinin-based therapies. Malaria is also a significant cause of life-threatening imported infection in the UK. It is vital for front line clinical staff involved in the assessment of acutely ill patients to be aware of the need for early diagnostic testing, malaria epidemiology, markers of severe infection and developments in antimalarial treatments to optimise patient management. The difference between a good and poor outcome is early diagnosis and treatment. Many of the challenges faced in the quest for global eradication, such as availability of appropriate diagnostic tests, and drug and insecticide resistance could also have future implications for imported malaria
Safety and high level efficiency of the combination malaria vaccine regimen of RTS,S/AS01B with ChAd-MVA vectored vaccines expressing ME-TRAP
No full textSafety and immunogenicity of a self-amplifying RNA vaccine against COVID-19: COVAC1, a phase I, dose-ranging trial
No full textBackground: Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is a novel technology formulated as a low dose vaccine against COVID-19. Methods: A phase I first-in-human dose-ranging trial of a saRNA COVID-19 vaccine candidate LNP-nCoVsaRNA, was conducted at Imperial Clinical Research Facility, and participating centres in London, UK, between 19th June to 28th October 2020. Participants received two intramuscular (IM) injections of LNP-nCoVsaRNA at six different dose levels, 0.1-10.0μg, given four weeks apart. An open-label dose escalation was followed by a dose evaluation. Solicited adverse events (AEs) were collected for one week from enrolment, with follow-up at regular intervals (1-8 weeks). The binding and neutralisation capacity of anti-SARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, immunoblot, SARS-CoV-2 pseudoneutralisation and wild type neutralisation assays. (The trial is registered: ISRCTN17072692, EudraCT 2020-001646-20). Findings: 192 healthy individuals with no history or serological evidence of COVID-19, aged 18-45 years were enrolled. The vaccine was well tolerated with no serious adverse events related to vaccination. Seroconversion at week six whether measured by ELISA or immunoblot was related to dose (both p<0.001), ranging from 8% (3/39; 0.1μg) to 61% (14/23; 10.0μg) in ELISA and 46% (18/39; 0.3μg) to 87% (20/23; 5.0μg and 10.0μg) in a post-hoc immunoblot assay. Geometric mean (GM) anti-S IgG concentrations ranged from 74 (95% CI, 45-119) at 0.1μg to 1023 (468-2236) ng/mL at 5.0μg (p<0.001) and was not higher at 10.0μg. Neutralisation of SARS-CoV-2 by participant sera was measurable in 15% (6/39; 0.1μg) to 48% (11/23; 5.0μg) depending on dose level received. Interpretation: Encapsulated saRNA is safe for clinical development, is immunogenic at low dose levels but failed to induce 100% seroconversion. Modifications to optimise humoral responses are required to realise its potential as an effective vaccine against SARS-CoV-2. Funding: This study was co-funded by grants and gifts from the Medical Research Council UKRI (MC_PC_19076), and the National Institute Health Research/Vaccine Task Force, Partners of Citadel and Citadel Securities, Sir Joseph Hotung Charitable Settlement, Jon Moulton Charity Trust, Pierre Andurand, Restore the Earth
COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2Research in context
No full textSummary: Background: Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is well tolerated and immunogenic in SARS-CoV-2 seronegative and seropositive individuals aged 18–75. Methods: A phase 2a expanded safety and immunogenicity study of a saRNA SARS-CoV-2 vaccine candidate LNP-nCoVsaRNA, was conducted at participating centres in the UK between 10th August 2020 and 30th July 2021. Participants received 1 μg then 10 μg of LNP-nCoVsaRNA, ∼14 weeks apart. Solicited adverse events (AEs) were collected for one week post-each vaccine, and unsolicited AEs throughout. Binding and neutralisating anti-SARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, and SARS-CoV-2 pseudoneutralisation assay. (The trial is registered: ISRCTN17072692, EudraCT 2020-001646-20). Findings: 216 healthy individuals (median age 51 years) received 1.0 μg followed by 10.0 μg of the vaccine. 28/216 participants were either known to have previous SARS-CoV2 infection and/or were positive for anti-Spike (S) IgG at baseline. Reactogenicity was as expected based on the reactions following licensed COVID-19 vaccines, and there were no serious AEs related to vaccination. 80% of baseline SARS-CoV-2 naïve individuals (147/183) seroconverted two weeks post second immunization, irrespective of age (18–75); 56% (102/183) had detectable neutralising antibodies. Almost all (28/31) SARS-CoV-2 positive individuals had increased S IgG binding antibodies following their first 1.0 μg dose with a ≥0.5log10 increase in 71% (22/31). Interpretation: Encapsulated saRNA was well tolerated and immunogenic in adults aged 18–75 years. Seroconversion rates in antigen naïve were higher than those reported in our dose-ranging study. Further work is required to determine if this difference is related to a longer dosing interval (14 vs. 4 weeks) or dosing with 1.0 μg followed by 10.0 μg. Boosting of S IgG antibodies was observed with a single 1.0 μg injection in those with pre-existing immune responses. Funding: Grants and gifts from the Medical Research Council UKRI (MC_PC_19076), the National Institute for Health Research/Vaccine Task Force, Partners of Citadel and Citadel Securities, Sir Joseph Hotung Charitable Settlement, Jon Moulton Charity Trust, Pierre Andurand, and Restore the Earth
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