A5035035385- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Bacterial Infections and Vaccines
- Pneumonia and Respiratory Infections
- Bacterial Genetics and Biotechnology
- Burkholderia infections and melioidosis
- SARS-CoV-2 detection and testing
- Respiratory Support and Mechanisms
- Viral Infections and Outbreaks Research
- Influenza Virus Research Studies
- Bacillus and Francisella bacterial research
- Animal Virus Infections Studies
- Poxvirus research and outbreaks
- Inhalation and Respiratory Drug Delivery
- Monoclonal and Polyclonal Antibodies Research
- Probiotics and Fermented Foods
- Respiratory viral infections research
- Peripheral Neuropathies and Disorders
- Yersinia bacterium, plague, ectoparasites research
- Microbial infections and disease research
- Subcritical and Supercritical Water Processes
- Protist diversity and phylogeny
- Infection Control and Ventilation
- COVID-19 epidemiological studies
- Vibrio bacteria research studies
UK Health Security Agency
2021-2024
Quadram Institute
2021-2024
Norwich Research Park
2021-2024
World Health Organization
2022-2023
Public Health England
2013-2022
Worthing Hospital
2017
Salisbury District Hospital
2001
Defence Science and Technology Laboratory
1987-1993
There is a vital need for authentic COVID-19 animal models to enable the pre-clinical evaluation of candidate vaccines and therapeutics. Here we report dose titration study SARS-CoV-2 in ferret model. After high (5 × 106 pfu) medium 104 virus delivered, intranasally, viral RNA shedding upper respiratory tract (URT) observed 6/6 animals, however, only 1/6 ferrets show similar signs after low 102 challenge. Following sequential culls pathological mild multifocal bronchopneumonia approximately...
A novel coronavirus, SARS-CoV-2, has been identified as the causative agent of current COVID-19 pandemic. Animal models, and in particular non-human primates, are essential to understand pathogenesis emerging diseases assess safety efficacy vaccines therapeutics. Here, we show that SARS-CoV-2 replicates upper lower respiratory tract causes pulmonary lesions both rhesus cynomolgus macaques. Immune responses against also similar species equivalent those reported milder infections convalescent...
ABSTRACT To support the licensure of a new and safer vaccine to protect people against smallpox, monkeypox model infection in cynomolgus macaques, which simulates smallpox humans, was used evaluate two vaccines, Acam2000 Imvamune, for protection disease. Animals vaccinated with single immunization Imvamune were not protected completely from severe and/or lethal infection, whereas those receiving either prime boost or completely. Additional parameters, including clinical observations,...
There is an urgent need for drugs, therapies and vaccines to be available protect the human population against COVID-19. One of first approaches taken in COVID-19 global response was consider repurposing licensed drugs. This commentary highlights extraordinary international collaborative effort independent researchers who have recently all come same conclusion—that chloroquine or hydroxchloroquine are unlikely provide clinical benefit
The mutation profile of the SARS-CoV-2 Omicron (lineage BA.1) variant posed a concern for naturally acquired and vaccine-induced immunity. We investigated ability prior infection with an early ancestral isolate (Australia/VIC01/2020, VIC01) to protect against disease caused by BA.1. established that BA.1 in naïve Syrian hamsters resulted less severe than comparable dose virus, fewer clinical signs including weight loss. present data show these observations were almost absent convalescent...
To better characterize the vaccine potential of Neisseria meningitidis transferrin binding proteins (Tbps), we have overexpressed TbpA and TbpB from isolate K454 in Escherichia coli. The ability to bind human was retained by both recombinant proteins, enabling purification affinity chromotography. Tbps were evaluated individually combination a mouse intraperitoneal-infection model determine their protect against meningococcal infection induce cross-reactive bactericidal antibodies. For first...
Several candidates for a vaccine against Burkholderia pseudomallei, the causal bacterium of melioidosis, have been developed, and rational approach is now needed to select advance testing in relevant nonhuman primate models human clinical trials. Development such was topic meeting United Kingdom March 2014 attended by international candidate developers, researchers, government health officials. The focus advancement vaccines prevention natural infection, rather than protection from...
Abstract In December 2019 an outbreak of coronavirus disease (COVID-19) emerged in Wuhan, China. The causative agent was subsequently identified and named severe acute respiratory syndrome 2 (SARS-CoV-2) which rapidly spread worldwide causing a pandemic. Currently there are no licensed vaccines or therapeutics available against SARS-CoV-2 but numerous candidate development repurposed drugs being tested the clinic. There is vital need for authentic COVID-19 animal models to further our...
Abstract An array of SARS-CoV-2 virus variants have been isolated, propagated and used in vitro assays, vivo animal studies human clinical trials. Observations working stocks suggest that sequential propagation Vero cells leads to critical changes the region furin cleavage site, which significantly reduce value stock for research studies. Serially propagating E6 rapid increases genetic while other cell lines (e.g. Vero/hSLAM) appears mitigate this risk thereby improving overall stability...
Clinical definitions of melioidosis and inhalation-acquired ( Burkholderia pseudomallei infection) are described together with the evidence used to develop these definitions. Such support accurate public health reporting, preparedness planning for deliberate B. release, design experimental models, categorization naturally acquired melioidosis.
In light of the recent outbreak Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range compounds currently available with broad antimicrobial activity tested against EBOV. Using live EBOV, eighteen candidate were screened vitro. The selected on a rational basis because their mechanisms action suggested that they had potential disrupt EBOV entry, replication or exit from cells displayed some previous tests. Nine...
Abstract Plague caused by the Gram-negative bacterium, Yersinia pestis, is still endemic in parts of world today. Protection against pneumonic plague essential to prevent development and spread epidemics. Despite this, there are currently no licensed vaccines western world. Here we describe means delivering biologically active vaccine antigens directly mucosal sites infection using highly stable microvesicles (outer membrane vesicles; OMVs) that naturally produced abundant harmless human...
The golden Syrian hamster (Mesocricetus auratus) is now commonly used in preclinical research for the study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and assessment vaccines, drugs therapeutics. Here, we show that hamsters inoculated via intranasal route with same infectious virus dose prototypical SARS-CoV-2 administered a different volume present clinical signs, weight loss viral shedding, reduced resulting severity disease similar to obtained by 500-fold...
To evaluate new vaccines when human efficacy studies are not possible, the FDA's "Animal Rule" requires well-characterized models of infection. Thus, in present study, early pathogenic events monkeypox infection nonhuman primates, a surrogate for variola virus infection, were characterized. Cynomolgus macaques exposed to aerosolized (10(5) PFU). Clinical observations, viral loads, immune responses, and pathological changes examined on days 2, 4, 6, 8, 10, 12 postchallenge. Viral DNA (vDNA)...
Abstract Background The aim was to carry out phase 4 international field-testing of the European Organisation for Research and Treatment Cancer (EORTC) breast reconstruction (BRECON) module. primary objective finalization its scale structure. Secondary objectives were evaluation reliability, validity, responsiveness, acceptability interpretability in patients with cancer undergoing mastectomy reconstruction. Methods EORTC module development guidelines followed. Patients recruited from 28...
There is an urgent requirement for safe and effective vaccines to prevent COVID-19. A concern the development of new viral potential induce vaccine-enhanced disease (VED). This was reported in several preclinical studies with both SARS-CoV-1 MERS but has not been SARS-CoV-2 vaccines. We have used ferrets rhesus macaques challenged assess VED animals vaccinated formaldehyde-inactivated (FIV) formulated Alhydrogel, compared a negative control vaccine. showed no evidence enhanced or given FIV...
In the summer of 2020, it became clear that genetic composition SARS-CoV-2 was changing rapidly. This highlighted by rapid emergence D614G mutation at time. autumn project entitled “Agility” initiated with funding from Coalition for Epidemic Preparedness Innovations (CEPI) to assess new variants SARS-CoV-2. The designed reach out and intercept swabs containing live variant viruses in order generate highly characterised master working stocks, biological consequences changes using both vitro...
Abstract New vaccines, therapeutics and immunity elicited by natural infection create evolutionary pressure on SARS-CoV-2 to evolve adapt evade vaccine-induced infection-elicited immunity. Vaccine developers thus find themselves in an “arms race” with the virus. The ongoing assessment of emerging variants remains essential as global community transitions from emergency response a long-term management plan. Here, we describe how authentic virus neutralisation assay using low passage clinical...
Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. The existence approximately 90 antigenically distinct capsular serotypes has greatly complicated the development an effective pneumococcal vaccine. Virulence-associated proteins common conserved among all types now represent best strategy to combat infections. PiuA PiaA are lipoprotein components two iron ABC transporters required for full virulence in mouse models infection. Here we describe study distribution...
Two-component regulatory systems are important regulators of virulence genes in a number bacteria. Genes encoding two-component regulator system, with homology to the phoP/phoQ system salmonella, were identified meningococcal genome. Allele replacement was used generate knock-out mutant component this and its phenotype examined. The displayed many differences protein profiles compared wild type, consistent it being gene-regulatory mutation. Many growth characteristics similar those phoP...