A5064040548- Influenza Virus Research Studies
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Respiratory viral infections research
- Animal Virus Infections Studies
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Tuberculosis Research and Epidemiology
- Viral gastroenteritis research and epidemiology
- Animal Disease Management and Epidemiology
- Glycosylation and Glycoproteins Research
- Immune responses and vaccinations
- SARS-CoV-2 and COVID-19 Research
- vaccines and immunoinformatics approaches
- Galectins and Cancer Biology
- Cell Adhesion Molecules Research
- Chemokine receptors and signaling
- Mycobacterium research and diagnosis
- Protein Tyrosine Phosphatases
- Virus-based gene therapy research
- Immunodeficiency and Autoimmune Disorders
- Microbial infections and disease research
- Diagnosis and treatment of tuberculosis
- Atherosclerosis and Cardiovascular Diseases
The Pirbright Institute
2016-2024
Medawar Building for Pathogen Research
2008-2017
University of Oxford
2007-2017
Max Planck Institute for Infection Biology
2011
Charité - Universitätsmedizin Berlin
2011
Jenner Institute
1999-2011
Centre for Human Genetics
2008
Cancer Research UK
2003-2008
Churchill Hospital
2007
John Radcliffe Hospital
2003
Abstract Boosting bacillus Calmette-Guérin (BCG)-primed mice with a recombinant adenovirus expressing Mycobacterium tuberculosis Ag 85A by different administration routes has very effects on protection against aerosol challenge M. tuberculosis. Mice boosted intradermally make strong splenic CD4 and CD8 Th1 cytokine responses to 85A, but show no change in lung mycobacterial burden over BCG primed animals. In contrast, intranasally greatly reduced much weaker response an increased purified...
Abstract There is need for effective and affordable vaccines against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a protein nanoparticle vaccine SARS-CoV-2. The based on display of coronavirus spike glycoprotein receptor-binding domain (RBD) synthetic virus-like particle (VLP) platform, SpyCatcher003-mi3, using SpyTag/SpyCatcher technology. Low doses RBD-SpyVLP in prime-boost regimen induce strong neutralising antibody response mice pigs that superior convalescent...
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...
M.bovis BCG vaccination against tuberculosis (TB) notoriously displays variable protective efficacy in different human populations. In non-human primate studies using rhesus macaques, despite efforts to standardise the model, we have also observed of upon subsequent experimental M. challenge. present head-to-head study, establish that standard parenteral immunisation varies among cohorts. This provides dynamic ranges for evaluation investigational vaccines, opportunities identifying possible...
Abstract SCID is a heterogeneous group of hereditary diseases. Mutations in the common γ-chain (γc) cytokine receptors, including those for IL-2, IL-4, IL-7, IL-9, and IL-15, are responsible an X-linked form disease, while mutations several other genes, Janus-associated kinase-3, may cause autosomal recessive forms SCID. We investigated first patient to be described with minimal cell surface expression leukocyte (CD45) Ag. CD45 abundant transmembrane tyrosine phosphatase, expressed on all...
Adjuvants are substances that enhance immune responses and thus improve the efficacy of vaccination. Few adjuvants available for use in humans, one is most commonly used (alum) often induces suboptimal immunity protection against many pathogens. There an obvious need to develop new improved adjuvants. We have therefore taken approach adjuvant discovery uses silico modeling structure-based drug-design. As proof-of-principle we chose target interaction chemokines CCL22 CCL17 with their...
Abstract Influenza A viruses are a major health threat to livestock and humans, causing considerable mortality, morbidity, economic loss. Current inactivated influenza vaccines strain specific new need be produced at frequent intervals combat newly arising virus strains, so that universal vaccine is highly desirable. We show pandemic H1N1 in which the hemagglutinin signal sequence has been suppressed (S-FLU), when administered pigs by aerosol can induce CD4 CD8 T cell immune responses blood,...
Abstract There is an urgent need for influenza vaccines providing broader protection that may decrease the annual immunization of human population. We investigated efficacy heterologous prime boost with chimpanzee adenovirus (ChAdOx2) and modified vaccinia Ankara (MVA) vectored vaccines, expressing conserved virus nucleoprotein (NP), matrix protein 1 (M1) neuraminidase (NA) in H1N1pdm09 pre-exposed pigs. compared intra-nasal, aerosol intra-muscular vaccine delivery against H3N2 challenge....
Abstract Influenza is a major health threat, and broadly protective influenza vaccine would be significant advance. Signal Minus FLU (S-FLU) candidate that limited to single cycle of replication, which induces strong cross-reactive T cell response but minimal Ab hemagglutinin after intranasal or aerosol administration. We tested whether an H3N2 S-FLU can protect pigs ferrets from heterosubtypic H1N1 challenge. Aerosol administration induced lung tissue-resident memory cells reduced pathology...
The pig is an important agricultural species and powerful biomedical model. We have established the pig, a large natural host animal for influenza with many physiological similarities to humans, as robust model testing therapeutic potential of monoclonal antibodies. Antibodies provide protection through neutralization recruitment innate effector functions Fc domain. However very little known about Fc-mediated porcine IgG subclasses. generated 8 subclasses two anti hemagglutinin characterized...
In the light of recent emergence multidrug-resistant and extensively drug-resistant strains Mycobacterium tuberculosis, epidemic tuberculosis (TB) in populations coinfected with human immunodeficiency virus, failure bovis bacillus Calmette-Guerin (BCG) to protect against disease, new vaccines TB are urgently needed. Two promising vaccine candidates recombinant DeltaureC hly(+) BCG (recBCG), which has been developed replace current strain, modified vaccinia virus Ankara (MVA) expressing M....
Background Adjuvants enhance or modify an immune response that is made to antigen. An antagonist of the chemokine CCR4 receptor can display adjuvant-like properties by diminishing ability CD4+CD25+ regulatory T cells (Tregs) down-regulate responses. Methodology Here, we have used protein modelling create a plausible model with aim using virtual screening identify potential small molecule antagonists. A combination homology and molecular docking was in order investigate lead compounds...
Convincing correlates of protective immunity against tuberculosis have been elusive. In BALB/c mice, intranasal immunization with a replication-deficient recombinant adenovirus expressing Mycobacterium antigen 85A (adenovirus-85A) induces lower respiratory tract pulmonary challenge tuberculosis, while intradermal adenovirus-85A does not. Here we report that expression the chemokine receptor CXCR6 on lung CD8 T lymphocytes, which is maintained for at least 3 months. CXCR6-positive...
BCG, the only licensed vaccine against tuberculosis (TB), provides geographically variable protection, an effect ascribed to exposure environmental mycobacteria (EM). Here we show that altering intestinal microbiota of mice by early-life infection with commensal bacterium Helicobacter hepaticus (Hh) increases their susceptibility challenge Mycobacterium (Mtb). Furthermore Hh-infected immunised parenterally recombinant subunit vaccine, human adenovirus type 5 expressing immunodominant antigen...
Tuberculosis remains a global health problem so that more effective vaccine than bacillus Calmette-Guérin is urgently needed. Cytomegaloviruses persist lifelong in vivo and induce powerful immune increasing ("inflationary") responses, making them attractive vectors. We have used an m1-m16-deleted recombinant murine CMV (MCMV) expressing Mycobacterium tuberculosis Ag 85A to show infection of mice with this significantly reduces the mycobacterial load after challenge M. tuberculosis, whereas...
ABSTRACT There is dire need for an effective and affordable vaccine against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a modular virus-like particle candidate displaying spike glycoprotein receptor-binding domain (RBD) using SpyTag/SpyCatcher technology (RBD-SpyVLP). Low doses of RBD-SpyVLP in prime-boost regimen induced strong neutralising antibody response mice pigs that was superior convalescent human sera. We evaluated quality ACE2 blocking neutralisation cell...
Nipah virus (NiV) is an emergent pathogen capable of causing acute respiratory illness and fatal encephalitis in pigs humans. A high fatality rate broad host tropism makes NiV a serious public animal health concern. There therefore urgent need for vaccines to protect animals In this study we investigated the immunogenicity bovine herpesvirus (BoHV-4) vectors expressing either attachment (G) or fusion (F) glycoproteins, BoHV-4-A-CMV-NiV-GΔTK BoHV-4-A-CMV-NiV-FΔTK, respectively pigs. The were...
In the light of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, we have developed a porcine (PRCV) model for in depth mechanistic evaluation pathogenesis, virology and immune responses this important family viruses. Pigs are large animal with similar physiology immunology to humans natural host PRCV. Four PRCV strains were investigated shown induce different degrees lung pathology. Importantly, although all four replicated equally well cell lines vitro upper tract...
Cattle possess three IgG subclasses. However, the key immune functions, including complement and NK cell activation, enhancement of phagocytosis, are not fully described for bovine IgG1, 2 3. We produced chimeric monoclonal antibodies (mAbs) consisting a defined variable region linked to constant regions 3, expressed His-tagged soluble recombinant Fc gamma receptors (FcγRs) IA (CD64), IIA (CD32A), III (CD16) Fcγ2R. Functional assays using bovinized mAbs were developed. IgG1 IgG3, but IgG2,...
Abstract We have investigated the role of specific components thymic stroma during development CD4 − 8 T cell precursors by separating and reaggregating precursor subsets with individual or combinations stromal cells. show that while CD25 + 44 is dependent upon a combination major histocompatibility complex (MHC) class II epithelial cells fibroblasts, their direct descendants, precursors, develop to stage in presence MHC alone. Thus, are last developmental be fibroblast support. In addition,...