ORCID Profile
0000-0002-5507-1725
Current Organisation
King's College London
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Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22545113
Abstract: Supplementary Table & Figure Legends
Publisher: Royal Society of Chemistry (RSC)
Date: 2010
DOI: 10.1039/C0CC03420G
Abstract: Statistical correlation of mass spectrum peak broadening with product dispersity in protein conjugation reactions allows more detailed characterization of putative therapeutic conjugates.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22545122.V1
Abstract: S2. T cell responses prior to SARS-CoV-2 vaccination dose 3.
Publisher: Springer Science and Business Media LLC
Date: 26-10-2020
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22545119
Abstract: S3. Boosted serological responses and persistent T cell responses following SARS-CoV-2 vaccination dose
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22545116
Abstract: S4. Local and systemic effects reported within 30 days after 3rd dose of COVID-19 vaccine in patients with solid and haematological cancers and healthy controls.
Publisher: Springer Science and Business Media LLC
Date: 06-10-2021
DOI: 10.1038/S41590-021-01049-2
Abstract: Despite extensive studies into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the effect of maternal infection on the neonate is unclear. To investigate this, we characterized the immunology of neonates born to mothers with confirmed SARS-CoV-2 infection during pregnancy. Here we show that maternal SARS-CoV-2 infection affects the neonatal immune system. Despite similar proportions of B cells, CD4
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22545113.V1
Abstract: Supplementary Table & Figure Legends
Publisher: Springer Science and Business Media LLC
Date: 17-08-2020
DOI: 10.1038/S41591-020-1038-6
Abstract: Improved understanding and management of COVID-19, a potentially life-threatening disease, could greatly reduce the threat posed by its etiologic agent, SARS-CoV-2. Toward this end, we have identified a core peripheral blood immune signature across 63 hospital-treated patients with COVID-19 who were otherwise highly heterogeneous. The signature includes discrete changes in B and myelomonocytic cell composition, profoundly altered T cell phenotypes, selective cytokine/chemokine upregulation and SARS-CoV-2-specific antibodies. Some signature traits identify links with other settings of immunoprotection and immunopathology others, including basophil and plasmacytoid dendritic cell depletion, correlate strongly with disease severity while a third set of traits, including a triad of IP-10, interleukin-10 and interleukin-6, anticipate subsequent clinical progression. Hence, contingent upon independent validation in other COVID-19 cohorts, in idual traits within this signature may collectively and in idually guide treatment options offer insights into COVID-19 pathogenesis and aid early, risk-based patient stratification that is particularly beneficial in phasic diseases such as COVID-19.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Public Library of Science (PLoS)
Date: 24-09-2020
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22545125
Abstract: S1. Waning serological responses to SARS-CoV-2 vaccination.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22545125.V1
Abstract: S1. Waning serological responses to SARS-CoV-2 vaccination.
Publisher: Elsevier BV
Date: 05-2022
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22545122
Abstract: S2. T cell responses prior to SARS-CoV-2 vaccination dose 3.
Publisher: Cold Spring Harbor Laboratory
Date: 17-03-2021
DOI: 10.1101/2021.03.17.21253131
Abstract: The efficacy and safety profile of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been definitively established in immunocompromised patient populations. Patients with a known cancer diagnosis were hitherto excluded from trials of the vaccines currently in clinical use. This study presents data on the safety and immune efficacy of the BNT162b2 (Pfizer-BioNTech) vaccine in 54 healthy controls and 151 mostly elderly patients with solid and haematological malignancies, respectively, and compares results for patients who were boosted with BNT162b2 at 3 weeks versus those who were not. Immune efficacy was measured as antibody seroconversion, T cell responses, and neutralisation of SARS-CoV-2 Wuhan strain and of a variant of concern (VOC) (B.1.1.7). We also collected safety data for the BNT162b2 vaccine up to 5 weeks following first dose. The vaccine was largely well tolerated. However, in contrast to its very high performance in healthy controls ( % efficacious), immune efficacy of a single inoculum in solid cancer patients was strikingly low (below 40%) and very low in haematological cancer patients (below 15%). Of note, efficacy in solid cancer patients was greatly and rapidly increased by boosting at 21-days (95% within 2 weeks of boost). Too few haematological cancer patients were boosted for clear conclusions to be drawn. Delayed boosting potentially leaves most solid and haematological cancer patients wholly or partially unprotected, with implications for their own health their environment and the evolution of VOC strains. Prompt boosting of solid cancer patients quickly overcomes the poor efficacy of the primary inoculum in solid cancer patients. Some cancer patients have been shown to exhibit sustained immune dysregulation, inefficient seroconversion and prolonged viral shedding as a consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Consequently, their exclusion and, in particular, the exclusion of patients receiving systemic anti-cancer therapies, from the registry trials of the 5 approved COVID-19 vaccines raises questions about the efficacy and safety of SARS-CoV-2 vaccination in this patient population. In addition, whilst the change in the UK’s dosing interval to 12-weeks aimed to maximise population coverage, it is unclear whether this strategy is appropriate for cancer patients and those on systemic anti-cancer therapies. We report that the RNA-based SARS-CoV-2 BNT162b2 vaccine administered in cancer patients was well tolerated, and we provide first insights into both antibody and T cell responses to the vaccine in an immunocompromised patient population. In cancer patients, one dose of 30ug of BNT162b2 yields poor vaccine efficacy, as measured by seroconversion rates, viral neutralisation capacity and T cell responses, at 3- and 5-weeks following the first inoculum. Patients with solid cancers exhibited a significantly greater response following a booster at 21-days. These data support prioritisation of cancer patients for an early (21-day) second dose of the BNT162b2 vaccine. Given the globally poor responses to vaccination in patients with haematological cancers, post-vaccination serological testing, creation of herd immunity around these patients using a strategy of ‘ring vaccination’, and careful follow-up should be prioritised.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22545119.V1
Abstract: S3. Boosted serological responses and persistent T cell responses following SARS-CoV-2 vaccination dose
Publisher: Springer Science and Business Media LLC
Date: 15-10-2021
DOI: 10.1038/S41564-021-00974-0
Abstract: COVID-19 vaccine design and vaccination rollout need to take into account a detailed understanding of antibody durability and cross-neutralizing potential against SARS-CoV-2 and emerging variants of concern (VOCs). Analyses of convalescent sera provide unique insights into antibody longevity and cross-neutralizing activity induced by variant spike proteins, which are putative vaccine candidates. Using sera from 38 in iduals infected in wave 1, we show that cross-neutralizing activity can be detected up to 305 days pos onset of symptoms, although sera were less potent against B.1.1.7 (Alpha) and B1.351 (Beta). Over time, despite a reduction in overall neutralization activity, differences in sera neutralization potency against SARS-CoV-2 and the Alpha and Beta variants decreased, which suggests that continued antibody maturation improves tolerance to spike mutations. We also compared the cross-neutralizing activity of wave 1 sera with sera from in iduals infected with the Alpha, the Beta or the B.1.617.2 (Delta) variants up to 79 days post onset of symptoms. While these sera neutralize the infecting VOC and parental virus to similar levels, cross-neutralization of different SARS-CoV-2 VOC lineages is reduced. These findings will inform the optimization of vaccines to protect against SARS-CoV-2 variants.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 28-05-2021
Abstract: SARS-CoV-2 spike N-terminal domain harbors a potent epitope that can be modulated by binding of natural linear tetrapyrroles.
Publisher: EMBO
Date: 09-2022
Abstract: The emergence of SARS‐CoV‐2 variants has exacerbated the COVID‐19 global health crisis. Thus far, all variants carry mutations in the spike glycoprotein, which is a critical determinant of viral transmission being responsible for attachment, receptor engagement and membrane fusion, and an important target of immunity. Variants frequently bear truncations of flexible loops in the N‐terminal domain (NTD) of spike the functional importance of these modifications has remained poorly characterised. We demonstrate that NTD deletions are important for efficient entry by the Alpha and Omicron variants and that this correlates with spike stability. Phylogenetic analysis reveals extensive NTD loop length polymorphisms across the sarbecoviruses, setting an evolutionary precedent for loop remodelling. Guided by these analyses, we demonstrate that variations in NTD loop length, alone, are sufficient to modulate virus entry. We propose that variations in NTD loop length act to fine‐tune spike this may provide a mechanism for SARS‐CoV‐2 to navigate a complex selection landscape encompassing optimisation of essential functionality, immune‐driven antigenic variation and ongoing adaptation to a new host.
Publisher: Cold Spring Harbor Laboratory
Date: 09-06-2020
DOI: 10.1101/2020.06.08.20125112
Abstract: Person-to-person transmission of SARS-CoV-2 virus has triggered a global emergency because of its potential to cause life-threatening Covid-19 disease. By comparison to paucisymptomatic virus clearance by most in iduals, Covid-19 has been proposed to reflect insufficient and/or pathologically exaggerated immune responses. Here we identify a consensus peripheral blood immune signature across 63 hospital-treated Covid-19 patients who were otherwise highly heterogeneous. The core signature conspicuously blended adaptive B cell responses typical of virus infection or vaccination with discrete traits hitherto associated with sepsis, including monocyte and dendritic cell d ening, and hyperactivation and depletion of discrete T cell subsets. This blending of immuno-protective and immuno-pathogenic potentials was exemplified by near-universal CXCL10/IP10 upregulation, as occurred in SARS1 and MERS. Moreover, specific parameters including CXCL10/IP10 over-expression, T cell proliferation, and basophil and plasmacytoid dendritic cell depletion correlated, often prognostically, with Covid-19 progression, collectively composing a resource to inform SARS-CoV-2 pathobiology and risk-based patient stratification.
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.C.6550859.V1
Abstract: This study offers longitudinal insight into the impact of three SARS-CoV-2 vaccinations on humoral and cellular immunity in patients with solid cancers, patients with hematologic malignancies, and persons without cancer. For all cohorts, virus-neutralizing immunity was significantly depleted over a period of up to 9 months following the second vaccine dose, the one striking exception being IL2 production by SARS-CoV-2 antigen-specific T cells. Immunity was restored by the third vaccine dose, except in a substantial number of patients with hematologic malignancy, for whom both cancer type and treatment schedule were associated with nonresponse. Thus, whereas most patients with myelodysplastic syndrome were conspicuously good responders, some patients with other hematologic malignancies receiving cancer therapies within 2 weeks of vaccination showed no seroconversion despite three vaccine doses. Moreover, SARS-CoV-2 exposure during the course of the study neither prevented immunity waning, even in healthy controls, nor guaranteed vaccine responsiveness. These data offer real-world human immunologic insights that can inform health policy for patients with cancer. Significance: Global health policy reliant on SARS-CoV-2 vaccine effectiveness is underpinned by our understanding of the durability of protection offered by sequential vaccinations and the efficacy of boosting, especially in immunocompromised patient populations who might constitute virus reservoirs. Here, we have: (i) clarified in patients with cancer the degree of waning of antibodies, serum neutralization titres against parental virus and variants of concern, and T-cell responses (ii) evaluated the immune response among patients with cancer to a third dose of COVID-19 vaccine and (iii) provided safety data following the third dose of the BNT162b2 COVID-19 vaccine in patients with cancer. /
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.C.6550859
Abstract: This study offers longitudinal insight into the impact of three SARS-CoV-2 vaccinations on humoral and cellular immunity in patients with solid cancers, patients with hematologic malignancies, and persons without cancer. For all cohorts, virus-neutralizing immunity was significantly depleted over a period of up to 9 months following the second vaccine dose, the one striking exception being IL2 production by SARS-CoV-2 antigen-specific T cells. Immunity was restored by the third vaccine dose, except in a substantial number of patients with hematologic malignancy, for whom both cancer type and treatment schedule were associated with nonresponse. Thus, whereas most patients with myelodysplastic syndrome were conspicuously good responders, some patients with other hematologic malignancies receiving cancer therapies within 2 weeks of vaccination showed no seroconversion despite three vaccine doses. Moreover, SARS-CoV-2 exposure during the course of the study neither prevented immunity waning, even in healthy controls, nor guaranteed vaccine responsiveness. These data offer real-world human immunologic insights that can inform health policy for patients with cancer. Significance: Global health policy reliant on SARS-CoV-2 vaccine effectiveness is underpinned by our understanding of the durability of protection offered by sequential vaccinations and the efficacy of boosting, especially in immunocompromised patient populations who might constitute virus reservoirs. Here, we have: (i) clarified in patients with cancer the degree of waning of antibodies, serum neutralization titres against parental virus and variants of concern, and T-cell responses (ii) evaluated the immune response among patients with cancer to a third dose of COVID-19 vaccine and (iii) provided safety data following the third dose of the BNT162b2 COVID-19 vaccine in patients with cancer. /
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2767-9764.22545116.V1
Abstract: S4. Local and systemic effects reported within 30 days after 3rd dose of COVID-19 vaccine in patients with solid and haematological cancers and healthy controls.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Cold Spring Harbor Laboratory
Date: 11-07-2020
DOI: 10.1101/2020.07.10.20150540
Abstract: Determine indications and clinical utility of SARS-CoV-2 serology testing in adults and children. Prospective evaluation of initial three weeks of a daily Monday to Friday pilot SARS-CoV-2 serology service for patients. Early post “first-wave” SARS-CoV-2 transmission period at single centre London teaching hospital that provides care to the local community, as well as regional and national referral pathways for specialist services. 110 (72 adults, 38 children, age range 0-83 years, 52.7% female (n=58)). Patient serum from vetted referrals tested on CE marked and internally validated lateral flow immunoassay (LFIA) (SureScreen Diagnostics) detecting antibodies to SARS-CoV-2 spike proteins, with result and clinical interpretation provided to the direct care team. Performance characteristics, source and nature of referrals, feasibility and clinical utility of the service, particularly the benefit for clinical decision-making. The LFIA was deemed suitable for clinical advice and decision making following evaluation with 310 serum s les from SARS-CoV-2 PCR positive patients and 300 pre-pandemic s les, giving a sensitivity and specificity of 96.1% and 99.3% respectively. For the pilot, 115 referrals were received leading to 113 tests performed on 108 participants (s le not available for two participants) paediatrics (n=35), medicine (n=69), surgery (n=2) and general practice (n=2). 43.4% participants (n=49) had detectable antibodies to SARS-CoV-2. There were three main indications for serology new acute presentations potentially triggered by recent COVID-19 infection e.g. PIMS-TS (n=26) and pulmonary embolism (n=5), potential missed diagnoses in context of a recent compatible illness (n=40), and making infection control and immunosuppression treatment decisions in persistently SARS-CoV-2 RNA PCR positive in iduals (n=6). This study shows acceptable performance characteristics, feasibility and clinical utility of a SARS-CoV-2 serology service using a rapid, inexpensive and portable assay for adults and children presenting with a range of clinical indications. Results correlated closely with a confirmatory in-house ELISA. The study showed the benefit of introducing a serology service where there is a reasonable pre-test probability, and the result can be linked with clinical advice or intervention. Experience thus far is that the volume of requests from hospital referral routes are manageable within existing clinical and laboratory services however, the demand from community referrals has not yet been assessed. Given recent evidence for a rapid decline in antibodies, particularly following mild infection, there is likely a limited window of opportunity to realise the benefit of serology testing for in iduals infected during the “first-wave” before they potentially fall below a measurable threshold. Rapidly expanding availability of serology services for NHS patients will also help understand the long-term implications of serostatus and prior infection in different patient groups, particularly before emergence of any “second-wave” outbreak or introduction of a vaccination programme. The mechanisms and utility of providing a SARS-CoV-2 (COVID-19) serology service is under evaluation. There are different technologies detecting antibodies against different SARS-CoV-2 proteins. Antibodies are known to appear from about 10 days after symptom onset but it is unclear how long they persist. A SARS-CoV-2 serology service using a validated lateral flow immunoassay measuring antibodies against spike protein can be rapidly introduced with clinical benefit demonstrated for a broad range of in iduals. Indications include ‘missed’ diagnoses where COVID-19 infection has been suspected but SARS-COV-2 RNA tests were either negative or not performed, conditions potentially triggered by COVID-19 such as pulmonary embolism, and predicting infectivity or immunity in patients with persistently detectable SARS-CoV-2 RNA. Testing is quick, simple to perform and inexpensive, however emerging evidence that antibodies fall rapidly particularly in mild disease, and the observed breadth of emerging indications highlight the urgent need for targeted testing with clinical interpretation provided on a case-by-case basis.
Publisher: American Association for Cancer Research (AACR)
Date: 17-11-2022
DOI: 10.1158/2767-9764.CRC-22-0298
Abstract: This study offers longitudinal insight into the impact of three SARS-CoV-2 vaccinations on humoral and cellular immunity in patients with solid cancers, patients with hematologic malignancies, and persons without cancer. For all cohorts, virus-neutralizing immunity was significantly depleted over a period of up to 9 months following the second vaccine dose, the one striking exception being IL2 production by SARS-CoV-2 antigen-specific T cells. Immunity was restored by the third vaccine dose, except in a substantial number of patients with hematologic malignancy, for whom both cancer type and treatment schedule were associated with nonresponse. Thus, whereas most patients with myelodysplastic syndrome were conspicuously good responders, some patients with other hematologic malignancies receiving cancer therapies within 2 weeks of vaccination showed no seroconversion despite three vaccine doses. Moreover, SARS-CoV-2 exposure during the course of the study neither prevented immunity waning, even in healthy controls, nor guaranteed vaccine responsiveness. These data offer real-world human immunologic insights that can inform health policy for patients with cancer. Global health policy reliant on SARS-CoV-2 vaccine effectiveness is underpinned by our understanding of the durability of protection offered by sequential vaccinations and the efficacy of boosting, especially in immunocompromised patient populations who might constitute virus reservoirs. Here, we have: (i) clarified in patients with cancer the degree of waning of antibodies, serum neutralization titres against parental virus and variants of concern, and T-cell responses (ii) evaluated the immune response among patients with cancer to a third dose of COVID-19 vaccine and (iii) provided safety data following the third dose of the BNT162b2 COVID-19 vaccine in patients with cancer.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Katie Doores.