A5008513278- SARS-CoV-2 and COVID-19 Research
- interferon and immune responses
- HIV Research and Treatment
- COVID-19 Clinical Research Studies
- RNA Research and Splicing
- vaccines and immunoinformatics approaches
- Animal Virus Infections Studies
- Immune Cell Function and Interaction
- Heparin-Induced Thrombocytopenia and Thrombosis
- RNA regulation and disease
- HIV/AIDS drug development and treatment
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Viral gastroenteritis research and epidemiology
- Pneumocystis jirovecii pneumonia detection and treatment
- Chronic Myeloid Leukemia Treatments
- CAR-T cell therapy research
- CRISPR and Genetic Engineering
- Drug-Induced Adverse Reactions
- Bone and Joint Diseases
- SARS-CoV-2 detection and testing
- Long-Term Effects of COVID-19
- Viral Infections and Vectors
- Immune Response and Inflammation
- COVID-19 and healthcare impacts
- Cancer Immunotherapy and Biomarkers
King's College London
2020-2023
University College London
2017-2020
Institute of Infection and Immunity
2020
Interaction of the SARS-CoV-2 Spike receptor binding domain (RBD) with ACE2 on host cells is essential for viral entry. RBD dominant target neutralizing antibodies, and several epitopes have been molecularly characterized. Analysis circulating variants has revealed mutations arising in RBD, N-terminal (NTD) S2 subunits Spike. To understand how these affect antigenicity, we isolated characterized >100 monoclonal antibodies targeting NTD, from SARS-CoV-2-infected individuals. Approximately 45%...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is the target for neutralizing antibodies elicited following both infection and vaccination. While extensive research has shown that receptor binding domain (RBD) and, to a lesser extent, N-terminal (NTD) are predominant targets antibodies, identification of epitopes beyond these regions important informing vaccine development understanding antibody-mediated immune escape. Here, we identify class broadly bind an epitope on...
BackgroundCOVID-19 vaccines have robust immunogenicity in the general population. However, data for individuals with immune-mediated inflammatory diseases who are taking immunosuppressants remains scarce. Our previously published cohort study showed that methotrexate, but not targeted biologics, impaired functional humoral immunity to a single dose of COVID-19 vaccine BNT162b2 (Pfizer-BioNTech), whereas cellular responses were similar. Here, we aimed assess immune following second...
HIV-1 must replicate in cells that are equipped to defend themselves from infection through intracellular innate immune systems. evades sensing encapsidated DNA synthesis and encodes accessory genes antagonize specific antiviral effectors. Here, we show both particle associated, expressed Vpr, the stimulatory effect of a variety pathogen associated molecular patterns by inhibiting IRF3 NF-κB nuclear transport. Phosphorylation at S396, but not S386, was also inhibited. We propose that, rather...
The interaction of the SARS–CoV–2 Spike receptor binding domain (RBD) with ACE2 on host cells is essential for viral entry. RBD dominant target neutralizing antibodies and several epitopes have been molecularly characterized. Analysis circulating variants has revealed mutations arising in RBD, N–terminal (NTD) S2 subunits Spike. To fully understand how these affect antigenicity Spike, we isolated characterized targeting beyond already identified epitopes. Using recombinant as a sorting bait,...
Interferons play a critical role in regulating host immune responses to SARS-CoV-2, but the interferon (IFN)-stimulated gene (ISG) effectors that inhibit SARS-CoV-2 are not well characterized. The IFN-inducible short isoform of human nuclear receptor coactivator 7 (NCOA7) inhibits endocytic virus entry, interacts with vacuolar ATPase, and promotes endo-lysosomal vesicle acidification lysosomal protease activity. Here, we used ectopic expression knockout demonstrate NCOA7 infection by as...
Although the antibody response to COVID-19 vaccination has been studied extensively at polyclonal level using immune sera, little reported on monoclonal level. Here, we isolate a panel of 44 anti-SARS-CoV-2 antibodies (mAbs) from an individual who received two doses ChAdOx1 nCoV-19 (AZD1222) vaccine 12-week interval. We show that, despite relatively low serum neutralization titer, Spike-reactive IgG+ B cells are still detectable 9 months post-boost. Furthermore, mAbs with potent neutralizing...
Abstract Interferons play a critical role in regulating host immune responses to SARS-CoV-2, but the interferon (IFN)-stimulated gene (ISG) effectors that inhibit SARS-CoV-2 are not well characterized. The IFN-inducible short isoform of human nuclear receptor coactivator 7 (NCOA7) inhibits endocytic virus entry, interacts with vacuolar ATPase, and promotes endo-lysosomal vesicle acidification lysosomal protease activity. Here, we used ectopic expression knockout demonstrate NCOA7 infection...
Abstract Collectin-11 is a soluble C-type lectin produced at epithelial surfaces to initiate pathogen elimination by complement. Given the respiratory epithelium source of CL-11 and downstream complement-pathway components, we investigated potential impact pathogenicity SARS-CoV-2. While SARS-CoV-2 spike trimer could bind trigger complement activation followed MAC formation, virus was resistant lysis. Surprisingly, production infected cells enhanced opsonisation but this effect fully...
Abstract HIV-1 must replicate in cells that are equipped to defend themselves from infection through intracellular innate immune systems. evades sensing encapsidated DNA synthesis and encodes accessory genes antagonize specific antiviral effectors. Here we show both particle associated, expressed Vpr, the stimulatory effect of a variety pathogen associated molecular patterns by inhibiting IRF3 NF-κB nuclear transport. Phosphorylation at S396, but not S386, was also inhibited. We propose...
Abstract Interferon (IFN) mobilizes a cellular anti-viral state by inducing the expression of IFN-stimulated genes (ISGs). Myxovirus resistance 2 (MX2/MxB) is an ISG that inhibits HIV-1 infection suppressing viral import into nucleus. The amino-terminal domain (NTD) MX2 plays essential role in inhibition and, here, we exploit proteomic screening to identify myosin light chain phosphatase (MLCP) components MYPT1 and PPP1CB as key NTD binding partners. Experimental depletion either protein, or...