ORCID Profile
0000-0003-2314-507X
Current Organisations
Oregon Health & Science University
,
Moderna
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Publisher: American Association for the Advancement of Science (AAAS)
Date: 21-06-2023
DOI: 10.1126/SCITRANSLMED.ADE3901
Abstract: Adenoviral-vectored vaccines are licensed for prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Ebola virus, but, for bacterial proteins, expression in a eukaryotic cell may affect the antigen’s localization and conformation or lead to unwanted glycosylation. Here, we investigated the potential use of an adenoviral-vectored vaccine platform for capsular group B meningococcus (MenB). Vector-based candidate vaccines expressing MenB antigen factor H binding protein (fHbp) were generated, and immunogenicity was assessed in mouse models, including the functional antibody response by serum bactericidal assay (SBA) using human complement. All adenovirus-based vaccine candidates induced high antigen-specific antibody and T cell responses. A single dose induced functional serum bactericidal responses with titers superior or equal to those induced by two doses of protein-based comparators, as well as longer persistence and a similar breadth. The fHbp transgene was further optimized for human use by incorporating a mutation abrogating binding to the human complement inhibitor factor H. The resulting vaccine candidate induced high and persistent SBA responses in transgenic mice expressing human factor H. The optimized transgene was inserted into the clinically relevant ChAdOx1 backbone, and this vaccine has now progressed to clinical development. The results of this preclinical vaccine development study underline the potential of vaccines based on genetic material to induce functional antibody responses against bacterial outer membrane proteins.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.VACCINE.2018.01.031
Abstract: Capsular group X N. meningitidis (MenX) has emerged as a cause of localized disease outbreaks in sub-Saharan Africa, but the human immune response following exposure to MenX antigens is poorly described. We therefore assessed the natural immunity against MenX in in iduals who were living in an area affected by a MenX outbreak during 2007 in Togo, West Africa. During 2009, 300 healthy in iduals (100 aged 3-5 years, 100 aged 13-19 years and 100 aged 20-25 years) were included in the study, and serum responses were compared with sera from age-matched controls from the U.K. and Burkina Faso. MenX serum bactericidal antibody (SBA) was measured using rabbit complement, and antibodies against MenX polysaccharide (XPS) and outer membrane vesicles (XOMVs) were quantified by ELISA. The proportion of Togolese in iduals with an SBA titer of ≥8 against the MenX strain was 29% (95% confidence interval (CI) 18-41) among those aged 3-5 years, 34% (95% CI 9-60) among those aged 13-19 years and 32% (95% CI 24-40) among those aged 20-25 years. These were significantly higher than observed in the control populations from the U.K (range 13-16%) and Burkina Faso (range 2-6%). In Togolese in iduals, the concentration of serum IgG against XPS was higher among the two older age groups as compared to the youngest age group. Antibody concentrations against MenX PS correlated significantly with SBA titers. This supports further development of a MenX PS based conjugate vaccine. Further studies are needed to verify the ability of MenX PS to induce SBA in humans.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 09-2021
Publisher: Springer Science and Business Media LLC
Date: 12-2021
DOI: 10.1038/S41590-021-01084-Z
Abstract: NP 105–113 -B*07:02-specific CD8 + T cell responses are considered among the most dominant in SARS-CoV-2-infected in iduals. We found strong association of this response with mild disease. Analysis of NP 105–113 -B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP 105–113 -B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP 105–113 -B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP 105–113 -B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.
Publisher: Wiley
Date: 19-03-2021
DOI: 10.1002/SKI2.19
Abstract: Many classifiers have been developed that can distinguish different types of skin lesions (e.g., benign nevi, melanoma) with varying degrees of success. 1–5 However, even successfully trained classifiers may perform poorly on images that include artefacts. While problems created by hair and ink markings have been published, quantitative measurements of blur, colour and lighting variations on classification accuracy has not yet been reported to our knowledge. We created a system that measures the impact of various artefacts on machine learning accuracy. Our objectives were to (1) quantitatively identify the most egregious artefacts and (2) demonstrate how to assess a classification algorithm's accuracy when input images include artefacts. We injected artefacts into dermatologic images using techniques that could be controlled with a single variable. This allows us to quantitatively evaluate the impact on the accuracy. We trained two convolutional neural networks on two different binary classification tasks and measured the impact on dermoscopy images over a range of parameter values. The area under the curve and specificity‐at‐a‐given‐sensitivity values were measured for each artefact induced at each parameter. General blur had the strongest negative effect on the melanoma versus other task. Conversely, shifting the hue towards blue had a more pronounced effect on the suspicious versus follow task. Classifiers should either mitigate artefacts or detect them. Images should be excluded from diagnosis/recommendation when artefacts are present in amounts outside the machine perceived quality range. Failure to do so will reduce accuracy and impede approval from regulatory agencies.
Publisher: Springer Science and Business Media LLC
Date: 17-12-2020
Publisher: Elsevier BV
Date: 12-2020
Publisher: Springer Science and Business Media LLC
Date: 10-03-2022
DOI: 10.1038/S41467-022-28898-1
Abstract: The trajectories of acquired immunity to severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We present a detailed longitudinal cohort study of UK healthcare workers prior to vaccination, presenting April-June 2020 with asymptomatic or symptomatic infection. Here we show a highly variable range of responses, some of which (T cell interferon-gamma ELISpot, N-specific antibody) wane over time, while others (spike-specific antibody, B cell memory ELISpot) are stable. We use integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling OverNight) to explore this heterogeneity. We identify a subgroup of participants with higher antibody responses and interferon-gamma ELISpot T cell responses, and a robust trajectory for longer term immunity associates with higher levels of neutralising antibodies against the infecting (Victoria) strain and also against variants B.1.1.7 (alpha) and B.1.351 (beta). These variable trajectories following early priming may define subsequent protection from severe disease from novel variants.
Publisher: Springer Science and Business Media LLC
Date: 07-2019
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 08-2020
Publisher: Springer Science and Business Media LLC
Date: 17-12-2020
Publisher: Springer Science and Business Media LLC
Date: 17-08-2021
DOI: 10.1038/S41467-021-25167-5
Abstract: The extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from natural infection in early 2020. We show that neutralization of the VOC compared to a reference isolate of the original circulating lineage, B, is reduced: more profoundly against B.1.351 than for B.1.1.7, and in responses to infection or a single dose of vaccine than to a second dose of vaccine. Importantly, high magnitude T cell responses are generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. Vaccination is required to generate high potency immune responses to protect against these and other emergent variants.
Publisher: Elsevier BV
Date: 2021
Publisher: MDPI AG
Date: 28-06-2021
DOI: 10.3390/MICROORGANISMS9071394
Abstract: Vi-polysaccharide conjugate vaccines are efficacious against typhoid fever in children living in endemic settings, their recent deployment is a promising step in the control of typhoid fever. However, there is currently no accepted correlate of protection. IgG and IgA antibodies generated in response to Vi conjugate or Vi plain polysaccharide vaccination are important but there are no definitive protective titre thresholds. We adapted a luminescence-based serum bactericidal activity (SBA) for use with S. Typhi and assessed whether bactericidal antibodies induced by either Vi tetanus toxoid conjugate (Vi-TT) or Vi plain polysaccharide (Vi-PS) were associated with protection in a controlled human infection model of typhoid fever. Both Vi-PS and Vi-TT induced significant increase in SBA titre after 28 days (Vi-PS p 0.0001, Vi-TT p = 0.003), however higher SBA titre at the point of challenge did not correlate with protection from infection or reduced symptom severity. We cannot eliminate the role of SBA as part of a multifactorial immune response which protects against infection, however, our results do not support a strong role for SBA as a mechanism of Vi vaccine mediated protection in the CHIM setting.
Publisher: Elsevier BV
Date: 2022
Publisher: Elsevier BV
Date: 11-2021
Publisher: Elsevier BV
Date: 03-2022
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for christina dold.