Emily Phung
A5009078261- SARS-CoV-2 and COVID-19 Research
- Respiratory viral infections research
- Viral gastroenteritis research and epidemiology
- Pneumonia and Respiratory Infections
- Animal Virus Infections Studies
- vaccines and immunoinformatics approaches
- Neonatal Respiratory Health Research
- SARS-CoV-2 detection and testing
- Monoclonal and Polyclonal Antibodies Research
- COVID-19 Clinical Research Studies
- Influenza Virus Research Studies
- Advanced biosensing and bioanalysis techniques
- Biochemical and Structural Characterization
- Viral Infections and Immunology Research
- Immunodeficiency and Autoimmune Disorders
- Tracheal and airway disorders
- Bacillus and Francisella bacterial research
- Immunotherapy and Immune Responses
- Virology and Viral Diseases
- Viral Infections and Outbreaks Research
- Congenital Diaphragmatic Hernia Studies
- Advanced Biosensing Techniques and Applications
- Virus-based gene therapy research
National Institute of Allergy and Infectious Diseases
2019-2024
National Institutes of Health
2019-2024
George Washington University
2019-2021
Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important evaluate nonhuman primates. Nonhuman primates received 10 or 100 μg mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein SARS-CoV-2, no vaccine. Antibody T-cell responses were assessed before upper- lower-airway challenge with SARS-CoV-2. Active genomes...
Building a better RSV vaccine Respiratory syncytial virus (RSV) causes severe respiratory disease, especially in infants and the elderly. However, attempts to produce effective human vaccines have largely been unsuccessful. Structure-based design has used generate an fusion glycoprotein stabilized its prefusion conformation (DS-Cav1). This immunogen is highly mice macaques. Crank et al. now report results of phase I clinical trial using DS-Cav1 molecule. Four weeks after immunization, these...
Defenses against SARS-CoV-2 variants Our key defense the COVID-19 pandemic is neutralizing antibodies virus elicited by natural infection or vaccination. Recent emerging viral have raised concern because of their potential to escape antibody neutralization. Wang et al . identified four from early-outbreak convalescent donors that are potent 23 variants, including concern, and characterized binding spike protein severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yuan examined...
Summary A SARS-CoV-2 vaccine is needed to control the global COVID-19 public health crisis. Atomic-level structures directed application of prefusion-stabilizing mutations that improved expression and immunogenicity betacoronavirus spike proteins. Using this established immunogen design, release sequences triggered immediate rapid manufacturing an mRNA expressing prefusion-stabilized trimer (mRNA-1273). Here, we show mRNA-1273 induces both potent neutralizing antibody CD8 T cell responses...
Abstract Antigens displayed on self-assembling nanoparticles can stimulate strong immune responses and have been playing an increasingly prominent role in structure-based vaccines. However, the development of such immunogens is often complicated by inefficiencies their production. To alleviate this issue, we developed a plug-and-play platform using spontaneous isopeptide-bond formation SpyTag:SpyCatcher system to display trimeric antigens nanoparticles, including 60-subunit Aquifex aeolicus...
Biotin-labeled molecular probes, comprising specific regions of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike, would be helpful in isolation and characterization antibodies targeting this recently emerged pathogen. Here, we design constructs incorporating an N-terminal purification tag, a site-specific protease-cleavage site, probe region interest, C-terminal sequence targeted by biotin ligase. Probe include full-length spike ectodomain as well various subregions,...
The COVID-19 pandemic highlights an urgent need for vaccines that confer protection from SARS-CoV-2 infection. One approach to effective vaccine may be through the display of spikes on surface virus-like particles, in a manner structurally mimicking native virus. Here we report development Newcastle disease particles (NDVLPs) displaying prefusion-stabilized spike ectodomain (S2P). Immunoassays with SARS-CoV-2-neutralizing antibodies revealed antigenicity S2P-NDVLP generally similar soluble...
There is currently no licensed vaccine for respiratory syncytial virus (RSV). Here, we assess the effect of RSV fusion protein (F) conformation on B cell responses in a post hoc comparison samples from DS-Cav1 [prefusion (pre-F)] and MEDI7510 [postfusion (post-F)] clinical trials. We compared magnitude quality serological across time points vaccines. measured A neutralization, F-binding immunoglobulin G titers, competition assays at week 0 (before vaccination) 4 (after to evaluate antibody...
The emergence of highly transmissible SARS-CoV-2 variants concern (VOC) that are resistant to therapeutic antibodies highlights the need for continuing discovery broadly reactive antibodies. We identify four receptor-binding domain targeting from three early-outbreak convalescent donors with potent neutralizing activity against 12 including B.1.1.7 and B.1.351 VOCs. Two them ultrapotent, sub-nanomolar neutralization titers (IC50 <0.0006 0.0102 μ g/mL; IC80 < 0.0006 0.0251 g/mL). define...
Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in children older adults. An effective vaccine must elicit neutralizing antibodies targeting the RSV fusion (F) protein, which exists two major conformations, pre-fusion (pre-F) post-fusion (post-F). Although 50% of surface is shared, pre-F contains highly neutralization-sensitive antigenic sites not present on post-F. Recent advancement several subunit F-based trials has spurred interest quantifying understanding...
An important consequence of infection with a SARS-CoV-2 variant is protective humoral immunity against other variants. However, the basis for such cross-protection at molecular level incompletely understood. Here, we characterized repertoire and epitope specificity antibodies elicited by Beta, Gamma WA1 ancestral variants assessed their cross-reactivity to these more recent Delta Omicron We developed method obtain immunoglobulin sequences concurrent rapid production functional assessment...
Biotin-labeled molecular probes, comprising specific regions of the SARS-CoV-2 spike, would be helpful in isolation and characterization antibodies targeting this recently emerged pathogen. To develop such we designed constructs incorporating an N-terminal purification tag, a site-specific protease-cleavage site, probe region interest, C-terminal sequence targeted by biotin ligase. Probe included full-length spike ectodomain as well various subregions, also mutants to eliminate recognition...
Respiratory syncytial virus (RSV) is a substantial cause of morbidity and mortality globally. A candidate RSV prefusion (pre-F)-stabilized subunit vaccine, DS-Cav1, has previously been shown to elicit potent durable neutralizing activity in phase 1 clinical trial healthy adults. Here, we used fluorescently labeled probes flow cytometry evaluate the antigen specificity phenotype F-specific B cells longitudinally after DS-Cav1 immunization. Peripheral blood mononuclear (PBMCs) collected at...
Abstract Antigens displayed on self-assembling nanoparticles can stimulate strong immune responses and have been playing an increasingly prominent role in structure-based vaccines. However, the development of such immunogens is often complicated by inefficiencies their production. To alleviate this issue, we developed a plug-and-play platform using spontaneous isopeptide-bond formation SpyTag:SpyCatcher system to display trimeric antigens nanoparticles, including 60-subunit Aquifex aeolicus...
Recurrent respiratory syncytial virus (RSV) infection requiring hospitalization is rare and the underlying mechanism unknown. We aimed to determine role of CD14-mediated immunity in pathogenesis recurrent RSV infection.We performed genotyping longitudinal immunophenotyping first patient with a genetic CD14 deficiency who developed infection. analyzed gene expression profiles interleukin (IL)-6 production by peripheral blood mononuclear cells response pre- post-fusion (F) protein. generated...
Summary Biotin-labeled molecular probes, comprising specific regions of the SARS-CoV-2 spike, would be helpful in isolation and characterization antibodies targeting this recently emerged pathogen. To develop such we designed constructs incorporating an N-terminal purification tag, a site-specific protease-cleavage site, probe region interest, C-terminal sequence targeted by biotin ligase. Probe included full-length spike ectodomain as well various subregions, also mutants to eliminate...
An important consequence of infection with a SARS-CoV-2 variant is protective humoral immunity against other variants. The basis for such cross-protection at the molecular level incompletely understood. Here we characterized repertoire and epitope specificity antibodies elicited by Beta, Gamma ancestral assessed their cross-reactivity to these more recent Delta Omicron We developed high-throughput approach obtain immunoglobulin sequences produce monoclonal functional assessment from single B...
An effective vaccine for RSV is an unrealized public health goal. Recently, a single dose of the prefusion-stabilized fusion (F) glycoprotein subunit (DS-Cav1) was shown to substantially increase serum neutralizing activity in healthy adults. To understand induced B-cell repertoire at single-cell level, we evaluated F-specific responses before and after vaccination six participants identified 555 clonal lineages. DS-Cav1-induced lineages recognized prefusion conformation F (pre-F) were...
Abstract Background Specific humoral response against pre-fusion (pre-F) conformation of respiratory syncytial virus (RSV) F protein has been proposed to play a role severe infection. We aimed analyze the association between serum IgG titers pre-F and post-fusion (post-F) conformations RSV life-threatening disease (LTD) in previously healthy infants. Methods Prospective cohort study including infants &lt; 12 months, hospitalized with first infection, 2017-2019. Patients were defined have...