A5017578863- Antimicrobial Peptides and Activities
- SARS-CoV-2 and COVID-19 Research
- Malaria Research and Control
- Animal Virus Infections Studies
- vaccines and immunoinformatics approaches
- RNA and protein synthesis mechanisms
- Biochemical and Structural Characterization
- Pediatric health and respiratory diseases
- COVID-19 Clinical Research Studies
- Mosquito-borne diseases and control
- HIV Research and Treatment
- Immune Response and Inflammation
- Invertebrate Immune Response Mechanisms
- Immunotherapy and Immune Responses
- Signaling Pathways in Disease
- Complement system in diseases
- Cell Adhesion Molecules Research
- Bacterial Infections and Vaccines
- Glycosylation and Glycoproteins Research
- Computational Drug Discovery Methods
- Antibiotic Resistance in Bacteria
- Protease and Inhibitor Mechanisms
- Pneumonia and Respiratory Infections
- Respiratory viral infections research
- Virus-based gene therapy research
University of Oxford
2019-2024
Jenner Institute
2019-2024
Guy's and St Thomas' NHS Foundation Trust
2021
St Thomas' Hospital
2021
NIHR Southampton Biomedical Research Centre
2021
University Hospital Southampton NHS Foundation Trust
2021
University of Southampton
2021
University of Bristol
2021
Newcastle University
2021
Bristol Hospital
2021
Vaccine development against the SARS-CoV-2 virus focuses on principal target of neutralizing immune response, spike (S) glycoprotein. Adenovirus-vectored vaccines offer an effective platform for delivery viral antigen, but it is important generation antibodies that they produce appropriately processed and assembled antigen mimics observed virus. Here, we describe structure, conformation, glycosylation S protein derived from adenovirus-vectored ChAdOx1 nCoV-19/AZD1222 vaccine. We demonstrate...
BackgroundDevelopment of an effective vaccine against the pathogenic blood-stage infection human malaria has proved challenging, and no candidate affected parasitemia following controlled (CHMI) with Plasmodium falciparum.MethodsWe undertook a phase I/IIa clinical trial in healthy adults United Kingdom RH5.1 recombinant protein vaccine, targeting P. falciparum reticulocyte-binding homolog 5 (RH5), formulated AS01B adjuvant. We assessed safety, immunogenicity, efficacy CHMI. Trial registered...
A blood-stage Plasmodium falciparum malaria vaccine would provide a second line of defence to complement partially effective or waning immunity conferred by the approved pre-erythrocytic vaccines. RH5.1 is soluble protein candidate for P falciparum, formulated with Matrix-M adjuvant assess safety and immunogenicity in malaria-endemic adult paediatric population first time.
Abstract Summary: AMPA is a web application for assessing the antimicrobial domains of proteins, with focus on design new drugs. The provides fast discovery patterns in proteins that can be used to develop peptide-based drugs against pathogens. Results are shown user-friendly graphical interface and downloaded as raw data later examination. Availability: freely available at http://tcoffee.crg.cat/apps/ampa. source code also web. Contact: marc.torrent@upf.edu; david.andreu@upf.edu...
Highlights•Human PfRH5 vaccination induces cross-reactive neutralizing antimalarial antibodies•Neutralizing human antibodies bind epitopes close to the basigin binding site•Some non-neutralizing potentiate those several malaria proteins•Potentiating slow erythrocyte invasion by a new epitope on PfRH5SummaryThe Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is leading target for next-generation vaccines against disease-causing blood-stage of malaria. However, little...
Abstract Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using single immunisation. Here, we compared immunogenicity one or two doses nCoV-19 both mice and pigs. Whilst dose induced antigen-specific antibody T cells responses, booster immunisation enhanced particularly pigs, with significant increase...
Reducing the mortality and morbidity associated with COVID-19 remains a global health priority. Vaccines have proven highly effective at preventing infection hospitalization, but efforts must continue to improve treatment options for those who still become seriously ill.
BackgroundAlthough recent epidemiological data suggest that pneumococci may contribute to the risk of SARS-CoV-2 disease, cases coinfection with Streptococcus pneumoniae in patients coronavirus disease 2019 (COVID-19) during hospitalization have been reported infrequently. This apparent contradiction be explained by interactions severe acute respiratory syndrome 2 (SARS-CoV-2) and upper airway, resulting escape from protective host immune responses.MethodsHere, we investigated relationship...
Abstract Understanding mechanisms of antibody synergy is important for vaccine design and cocktail development. Examples between antibodies are well-documented, but the underlying these relationships often remain poorly understood. The leading blood-stage malaria candidate, CyRPA, essential invasion Plasmodium falciparum into human erythrocytes. Here we present a panel anti-CyRPA monoclonal that strongly inhibit parasite growth in vitro assays. Structural studies show growth-inhibitory bind...
Antimicrobial proteins and peptides (AMPs) are important effectors of the innate immune system that play a vital role in prevention infections. Recent advances have highlighted similarity between AMPs amyloid proteins. Using Eosinophil Cationic Protein as model, we rationalized structure-activity relationships aggregation antimicrobial activity. Our results show how protein can induce bacteria agglutination cell death. confocal total internal reflection fluorescence microscopy tracked...
Abstract Reticulocyte-binding protein homologue 5 (RH5), a leading blood-stage Plasmodium falciparum malaria vaccine target, interacts with cysteine-rich protective antigen (CyRPA) and RH5-interacting (RIPR) to form an essential heterotrimeric “RCR-complex”. We investigate whether RCR-complex vaccination can improve upon RH5 alone. Using monoclonal antibodies (mAbs) we show that parasite growth-inhibitory epitopes on each are surface-exposed the mAb pairs targeting different antigens...
Highlights•Inhibitory antibodies from RH5.1/AS01B vaccinees target the RH5 α-helical core•A truncated and thermostabilized RH5.2 immunogen induces more potent antibodies•Bioconjugation of to VLPs enhances antibody immunogenicity in rodents•RH5.2-VLP/Matrix-M highest functional antimalarial ratsSummaryPlasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is a leading blood-stage malaria vaccine antigen target, currently phase 2b clinical trial as full-length soluble...
ABSTRACT Antimicrobial proteins and peptides (AMPs) are essential effectors of innate immunity, acting as a first line defense against bacterial infections. Many AMPs exhibit high affinity for cell wall structures such lipopolysaccharide (LPS), potent endotoxin able to induce sepsis. Hence, understanding how can interact with neutralize LPS is special relevance human health. Eosinophil cationic protein (ECP) an eosinophil secreted activity both Gram-negative Gram-positive bacteria. ECP has...
ABSTRACT There is an urgent need to develop new agents against mycobacterial infections, such as tuberculosis and other respiratory tract or skin affections. In this study, we have tested two human antimicrobial RNases mycobacteria. RNase 3, also called the eosinophil cationic protein, 7 are small proteins secreted by innate cells during host defense. Both induced upon infection displaying a wide range of antipathogen activities. particular, they released leukocytes epithelial cells,...
Eradication of established biofilm communities pathogenic Gram-negative species is one the pending challenges for development new antimicrobial agents. In particular, Pseudomonas aeruginosa main dreaded nosocomial species, with a tendency to form organized microbial that offer an enhanced resistance conventional antibiotics. We describe here engineered peptide (AMP) which combines bactericidal activity high bacterial cell agglutination and lipopolysaccharide (LPS) affinity. The...
Abstract The development of a highly effective vaccine against the pathogenic blood-stage infection human malaria will require delivery platform that can induce an antibody response both maximal quantity and functional quality. One strategy to achieve this includes presenting antigens immune system on virus-like particles (VLPs). Here we sought improve design Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) antigen, which is currently in Phase 2 clinical trial as...
Human Ribonuclease 6 is a secreted protein belonging to the ribonuclease A (RNaseA) superfamily, vertebrate specific family suggested arise with an ancestral host defense role. Tissue distribution analysis revealed its expression in innate cell types, showing abundance monocytes and neutrophils. Recent evidence of induction by bacterial infection antipathogen function vivo. In our laboratory, antimicrobial properties have been evaluated against Gram-negative Gram-positive species mechanism...
Procollagen C-proteinase enhancer-1 (PCPE-1) is a secreted protein that specifically accelerates proteolytic release of the C-propeptides from fibrillar procollagens, crucial step in fibril assembly. As such, it potential therapeutic target to improve tissue repair and prevent fibrosis, major cause mortality worldwide. Here we present crystal structure active CUB1CUB2 fragment PCPE-1 bound C-propeptide trimer procollagen III (CPIII). This shows two CUB domains bind different chains CPIII...
Vertebrate secreted RNases (ribonucleases) are small proteins that play important roles in RNA metabolism, angiogenesis or host defence. In the present study we describe antimicrobial properties of N-terminal domain hcRNases (human canonical RNases) and show their activity is well conserved among lineage. Furthermore, all domains display a similar mechanism, characterized by bacteria agglutination followed membrane permeabilization. The results that, for hcRNases, (i) retained at N-terminus...
Abstract Vaccine development against the SARS-CoV-2 virus focuses on principal target of neutralizing immune response, spike (S) glycoprotein. Adenovirus-vectored vaccines offer an effective platform for delivery viral antigen, but it is important generation antibodies that they produce appropriately processed and assembled antigen mimics observed virus. Here, we describe structure, conformation glycosylation S protein derived from adenovirus-vectored ChAdOx1 nCoV-19/AZD1222 vaccine. We...