- Viral gastroenteritis research and epidemiology
- Clostridium difficile and Clostridium perfringens research
- Respiratory viral infections research
- Influenza Virus Research Studies
- Immune Response and Inflammation
- Viral Infections and Outbreaks Research
- Mosquito-borne diseases and control
- Toxin Mechanisms and Immunotoxins
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Microscopic Colitis
- Viral Infections and Vectors
- Herpesvirus Infections and Treatments
- Immune Cell Function and Interaction
- HIV/AIDS Research and Interventions
- Animal Virus Infections Studies
- SARS-CoV-2 and COVID-19 Research
- Family and Disability Support Research
- T-cell and B-cell Immunology
- Pneumonia and Respiratory Infections
- Assistive Technology in Communication and Mobility
- PARP inhibition in cancer therapy
- Systemic Lupus Erythematosus Research
- COVID-19 diagnosis using AI
- Cerebral Palsy and Movement Disorders
United States Military Academy
2004-2022
Merck & Co., Inc., Rahway, NJ, USA (United States)
2010-2022
Great Ormond Street Hospital for Children NHS Foundation Trust
2021
Merck (Japan)
2015
The goal of an AIDS vaccine regimen designed to induce cellular immune responses should be reduce the viral set point and preserve memory CD4 lymphocytes. Here we investigated whether vaccine-induced immunity in absence any Env-specific antibodies can control replication following multiple low-dose challenges with highly pathogenic SIVmac239 isolate. Eight Mamu-A*01-positive Indian rhesus macaques were vaccinated simian immunodeficiency virus (SIV) gag, tat, rev, nef using a DNA...
Expression of several major histocompatibility complex (MHC) class I alleles is associated with a protective effect against disease progression in both human immunodeficiency virus type 1 and simian infection. To understand the mechanism underlying this effect, we investigated expression MHC allele Mamu-A*01 simian-human (SHIV) infection, one models for evaluation AIDS vaccine candidates. We found that was significantly delayed Mamu-A*01-positive rhesus monkeys infected highly pathogenic...
Conventional influenza vaccines can prevent infection, but their efficacy depends on the degree of antigenic "match" between strains used for vaccine preparation and those circulating in population. A universal based invariant regions virus, able to provide broadly cross-reactive protection, without requiring continuous manufacturing update, would solve a major medical need. Since temporal geographical dominance virus type and/or subtype (A/H3, A/H1, or B) cannot yet be predicted, vaccine,...
Monitoring antigen-specific memory B cells and the antibodies they encode is important for understanding specificity, breadth duration of immune response to an infection or vaccination. The isolated could further help design vaccine antigens raising relevant protective responses. However, developing assays measure isolate technically challenging due low frequencies these that exist in circulating blood. Here, we describe a flow cytometry method identify dengue envelope-specific using labeled...
To investigate a vaccine technology with potential to protect against coronavirus disease 2019 (COVID-19) and reduce transmission of severe acute respiratory syndrome 2 (SARS-CoV-2) single dose, we developed SARS-CoV-2 candidate using the live vesicular stomatitis virus (VSV) chimeric approach previously used develop licensed Ebola vaccine.We generated replication-competent VSV-SARS-CoV-2 by replacing VSV glycoprotein (G) gene coding sequence for Spike (S). Immunogenicity lead...
Clostridium difficile infections (CDI) are a leading cause of nosocomial diarrhea in the developed world. The main virulence factors bacterium large clostridial toxins (LCTs), TcdA and TcdB, which largely responsible for symptoms disease. Recent outbreaks CDI have been associated with emergence hypervirulent strains, such as NAP1/BI/027, many strains also produce third toxin, binary toxin (CDTa CDTb). These increased morbidity higher mortality. Here we present pre-clinical data describing...
There is still no safe and effective vaccine against dengue virus infection. Epidemics of infection are increasingly a threat to human health around the world. Antibodies generated in response have been shown impact disease development effectiveness vaccine. In this study, we investigated monoclonal antibody responses an experimental rhesus macaques. Variable regions both heavy chain (VH) light (VL) were cloned from single antibody-secreting B cells. A total 780 antibodies (mAbs) composed...
Infection with Respiratory Syncytial Virus (RSV) causes both upper and lower respiratory tract disease in humans, leading to significant morbidity mortality young children older adults. Currently, there is no licensed vaccine available, therapeutic options are limited. During the infection process, type I viral fusion (F) glycoprotein on surface of RSV particle rearranges from a metastable prefusion conformation highly stable postfusion form. In people naturally infected RSV, most potent...
Pathogenic bacteria produce several virulence factors that help them establish infection in permissive hosts. Bacterial toxins are a major class of and hence attractive therapeutic targets for vaccine development. Here, we describe the development rapid, sensitive, high-throughput assay can be used as versatile platform to measure activities bacterial toxins. We have exploited ability these cause cell death via apoptosis sensitive cultured lines readout measuring toxin activity. Caspases...
Clostridium difficile produces two major virulence toxins, toxin A (TcdA) and B (TcdB). Antitoxin antibodies, especially neutralizing have been shown to be associated with a lower incidence of C. infection (CDI) recurrence, antibody levels are predictive asymptomatic colonization. The development an assay detect the presence antibodies in animal human sera for evaluation vaccine efficacy is highly desired. We developed such assay, which allows quantification effect toxins on eukaryotic cells...
ABSTRACT Clostridium difficile strains producing binary toxin, in addition to toxin A (TcdA) and B (TcdB), have been associated with more severe disease increased recurrence of C. infection recent outbreaks. Binary comprises two subunits (CDTa CDTb) catalyzes the ADP-ribosylation globular actin (G-actin), which leads depolymerization filamentous (F-actin) filaments. robust assay is highly desirable for detecting cytotoxic effect presence neutralizing antibodies animal human sera evaluate...
Abstract Monitoring antigen-specific memory B cells and the antibodies they encode is important for understanding specificity, breadth duration of immune response to an infection or vaccination. The isolated could further help design vaccine antigens raising relevant protective responses. However, developing assays measure isolate antigen specific technically challenging due low frequencies these that exist in circulating blood. Here we describe a method develop direct flow cytometric assay...
Glycoprotein E (gE) and glycoprotein I (gI) are expressed as a heterodimer on the surface of Herpes simplex virus (HSV). binds Fc domain immunoglobulin G (IgG) inhibits activities mediated by IgG domain, contributing to immune evasion HSV. It has been reported that HSV type 1 gE (gE-1) is capable binding monomer in heterodimeric complex with gI, having 50- to100-fold greater affinity for than alone. We report production both soluble form 2 (gE-2) HSV-2 gE/gI (gE-2/gI-2). Characterization...
<h3>Introduction</h3> The primary goal of selective dorsal rhizotomy (SDR) is improvement in functional mobility. Outcomes at 2 years after single-level SDR and rehabilitation are presented for ambulatory children (Gross Motor Classification System (GMFCS) levels II III) with bilateral spastic cerebral palsy. <h3>Method</h3> Data from 82 children, GMFCS level (n=26) III (n=56) who underwent follow-up were analysed. Mean age (SD; range) surgery was 6yrs 7m (2yrs 2m; 2yrs 9m to 13yrs 8m)....