
Julia Laura MarshallUniversity of Oxford | OX · Nuffield Department of Clinical Medicine
Julia Laura Marshall
Bachelor of Medicine (Hons), Bachelor of Science
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51
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Publications (51)
Background
Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection continue to rise in the Arabian Peninsula 7 years after it was first described in Saudi Arabia. MERS-CoV poses a significant risk to public health security because of an absence of currently available effective countermeasures. We aimed to assess the safety and im...
Background
There is an urgent need for an effective tuberculosis (TB) vaccine. Heterologous prime–boost regimens induce potent cellular immunity. MVA85A is a candidate TB vaccine. This phase I clinical trial was designed to evaluate whether alternating aerosol and intradermal vaccination routes would boost cellular immunity to the Mycobacterium tub...
Background
Infection with Mycobacterium ulcerans causes slowly progressive skin lesions known as Buruli ulcer (BU). An M. ulcerans controlled human infection model (MuCHIM) is likely to accelerate our understanding of this otherwise neglected disease, and may be an efficient platform for testing vaccines and other interventions. The aim of this stu...
Background Induction of CD8 ⁺ T-cells using viral vectors is a promising strategy in developing effective vaccines against pre-erythrocytic malaria. A recent comparative assessment of candidate antigens using this approach in a mouse model had identified Liver Stage Antigen 1 (LSA1) and Liver Stage Associated Protein 2 (LSAP2) as more protective th...
Critical knowledge gaps have impeded progress towards reducing the global burden of disease due to Mycobacterium ulcerans , the cause of the neglected tropical disease Buruli ulcer (BU). Development of a controlled human infection model of BU has been proposed as an experimental platform to explore host-pathogen interactions and evaluate tools for...
Background: Novel vaccines targeting the world’s deadliest pathogen Mycobacterium tuberculosis (Mtb) are urgently needed as the efficacy of the Bacillus Calmette–Guérin (BCG) vaccine in its current use is limited. HLA-E is a virtually monomorphic unconventional antigen presentation molecule, and HLA-E-restricted Mtb-specific CD8⁺ T cells can contro...
Novel vaccines targeting the world’s deadliest pathogen Mycobacterium tuberculosis ( Mtb ) are urgently needed as the efficacy of the Bacillus Calmette–Guérin (BCG) vaccine in its current use is limited. HLA-E is a virtually monomorphic unconventional antigen presentation molecule and HLA-E restricted Mtb specific CD8 ⁺ T cells can control intracel...
Plain language summary
This paper describes a provisional clinical protocol for the pilot human challenge model of Mycobacterium ulcerans infection, which causes the skin disease 'Buruli ulcer' (BU). BU is typically painless and begins as a small area of redness or swelling, and is curable with antibiotics. If the diagnosis is delayed, it can resul...
Critical scientific questions remain regarding infection with Mycobacterium ulcerans, the organism responsible for the neglected tropical disease, Buruli ulcer (BU). A controlled human infection model has the potential to accelerate our knowledge of the immunological correlates of disease, to test prophylactic interventions and novel therapeutics....
Background
A SARS-CoV-2 controlled human infection model (CHIM) has been successfully established in seronegative individuals using a dose of 1×10¹ 50% tissue culture infectious dose (TCID50) pre-alpha SARS-CoV-2 virus. Given the increasing prevalence of seropositivity to SARS-CoV-2, a CHIM that could be used for vaccine development will need to in...
Critical scientific questions remain regarding infection with Mycobacterium ulcerans, the organism responsible for the neglected tropical disease, Buruli ulcer (BU). A controlled human infection model has the potential to accelerate our knowledge of the immunological correlates of disease, to test prophylactic interventions and novel therapeutics....
Aims
The influence of human factors on safety in healthcare settings is well established, with targeted interventions reducing risk and enhancing team performance. In experimental and early phase clinical research participant safety is paramount and safeguarded by guidelines, protocolized care and staff training; however, the real‐world interaction...
Introduction
Controlled human infection models (CHIMs) involve the deliberate exposure of individuals to a pathogen in a controlled environment. Respiratory organism CHIMs have been utilised to further understanding on the kinetics of infection or host-pathogen immunobiology plus enabling expedited testing of vaccines and therapeutics. A SARS-CoV-2...
Critical knowledge gaps regarding infection with Mycobacterium ulcerans, the cause of Buruli ulcer (BU), have impeded development of new therapeutic approaches and vaccines for prevention of this neglected tropical disease. Here, we review the current understanding of host–pathogen interactions and correlates of immune protection to explore the cas...
Multiple immunological mechanisms interact to protect against Mycobacterium tuberculosis (M.tb) infection and/or tuberculosis (TB) disease. However, development of a much-needed new and effective TB vaccine is hindered by the lack of validated correlates of protection. The identification of correlates of protection would facilitate the rational des...
Bacille Calmette-Guérin (BCG), the only currently licenced tuberculosis vaccine, may exert beneficial non-specific effects (NSE) in reducing infant mortality. We conducted a randomised controlled clinical study in healthy UK adults to evaluate potential NSE using functional in-vitro growth inhibition assays (GIAs) as a surrogate of protection from...
Background
COVID-19 vaccine supply shortages are causing concerns about compromised immunity in some countries as the interval between the first and second dose becomes longer. Conversely, countries with no supply constraints are considering administering a third dose. We assessed the persistence of immunogenicity after a single dose of ChAdOx1 nCo...
p>More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we...
The immunogenicity of the candidate tuberculosis (TB) vaccine MVA85A may be enhanced by aerosol delivery. Intradermal administration was shown to be safe in adults with latent TB infection (LTBI), but data are lacking for aerosol-delivered candidate TB vaccines in this population. We carried out a Phase I trial to evaluate the safety and immunogeni...
Background The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first d...
Background
A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials.
Methods
This analysis includes dat...
Older adults are at higher risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often poorer in older adults as a result of immunosenescence. We recently reported the immunogenicity of a novel viral vectored vaccine, ChAdOx1...
Background
Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpa...
Background
The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2.
Methods
We did a phase 1/2, single-blind, randomised controlled trial in five t...
ICS gating strategy.
Lymphocytes were gated on a forward scatter area (FSC-A) versus side scatter (SSC) (a). Next, duplets were excluded on a forward scatter height (FSC-H) versus FSC-A (b). CD14+ and CD19+ cells were excluded by gating on CD3+ Dump− (CD14 and CD19) (c). For BAL samples, dead cells were also excluded. Within CD3+ lymphocytes, CD4+...
Solicited AEs by volunteer, after each vaccination.
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The numbers of participants within each group reporting each related AE.
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Systemic AEs by group, by vaccination, and by severity.
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Respiratory AEs by group, by vaccination, and by severity.
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WB intracellular cytokines statistical analysis: AUC—85A.
Mann–Whitney test (AUC medians).
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Total CD3+ T lymphocytes detected in D7 and D35 BAL by group.
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Clinical trial protocol.
A phase I trial evaluating mucosal administration of a candidate TB vaccine, MVA85A, as a way to induce potent local cellular immune responses and avoid anti-vector immunity.
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Baseline characteristics.
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Solicited AEs by volunteer, by group.
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ELISpot responses statistical analysis: AUC.
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WB intracellular cytokines statistical analysis: AUC—MVA.
Mann–Whitney test (AUC medians).
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Median percent change of FEV1 and FVC from baseline at each time point in the 7 days following vaccination by group.
Baseline spirometry taken from the volunteer’s D0 pre-vaccination reading in all panels. Median with interquartile range. FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity.
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WB intracellular cytokines statistical analysis: AUC.
One-way ANOVA (Kruskal–Wallis) adjusted for multiple comparisons.
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Ag85A- and MVA-specific serum IgA response for Groups 1, 2, and 3.
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Group A streptococcus (GAS) is the most common bacterial cause of sore throat. School-age children bear the highest burden of GAS pharyngitis. Accurate diagnosis is difficult: the majority of sore throats are viral in origin, culture-based identification of GAS requires 24--48 hours, and up to 15% of children are asymptomatic throat carriers of GAS...
Several possible functions have been proposed for antiphonal duetting in birds, including pair-bond maintenance, cooperative territorial defence and acoustic mate guarding. Previous work has suggested that duetting in magpie-larks was consistent with both defence of the territory and guarding the mate against usurpation. We conducted playback exper...