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Principal Investigator: Wing Pui Kong
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2023
Award: $2,480,852
Funding agency: National Institute of Allergy and Infectious Diseases
The Virology Core has collaborated with other intramural NIAID labs help to develop a pan-coronaviruses spike protein subunit vaccine and a re-emerging infectious diseases, EV-D68.
During the past year, we focused on developing the vaccine vaccines against most subecoviruses or beta-coronaviruses. We successfully constructed hybrid immunogens of the MERS-CoV Spike or the subunits of the spike, RBD or S1, fused with SARS-CoV2 spike or its subunit proteins tandemly. The hybrid immunogens contained both epitopes of the two viruses in one protein. In addition, we also tried to load the target immunogen proteins on various VLPs to form potentially more immunogenic vaccine candidates. The purified hybrid proteins, loaded VLPs and the plasmid DNA encoding those immunogens were tested in animals. Small animal studies for evaluating the potency of the candidates are actively on-going. Another round of designs and modification are on-going and evaluation of the modified vaccine designs in animal models will perform soon.
For continuing isolation of the high potency and breadth of anti-Coronavirus monoclonal antibody (mAb) from immunized animals, we are using specific spike subunit probes (S2P spike, S1 or RBD) for screening and cloning B cells from Covid-19 vaccine immunized animals. Some mAbs specific binding to various Covid-19 emerging variants and other coronaviruses have been successfully isolated. We continue doing more screening assays, including sequencing, EM and pseudoviruses neutralizing of covid-19 variants and different coronaviruses to characterize all those mAbs.
In addition, we involved in vaccine development of re-emerging infectious diseases. One recent target is the enterovirus D68 (EV-D68) which causes severe respiratory illness in children. we demonstrate that EV-D68 virus-like particle (VLP) vaccines elicit a protective neutralizing antibody against homologous and heterologous EV-D68 subclades. VLP based on a B1 subclade 2014 outbreak strain elicited comparable B1 EV-D68 neutralizing activity as an inactivated viral particle vaccine in mice. Our results suggest that both vaccine strain and adjuvant selection are critical elements for improving the breadth of protective immunity against EV-D68.
Terms: <0-11 years old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><Adjuvant><Animal Model><Animal Models and Related Studies><Animals><Antibodies><Antigenic Determinants><Antigens><Assay><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Binding><Binding Determinants><Bioassay><Biologic Assays><Biological Assay><COVID-19><COVID-19 vaccine><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID19><COVID19 vaccine><COVID19 virus><CV-19><CV19><Child><Child Youth><Children (0-21)><Clinical Treatment Moab><Cloning><CoV S protein><CoV glycoprotein S><CoV spike glycoprotein><CoV spike protein><CoV-2><CoV2><Collaborations><Coronaviridae><Coronaviridae Infections><Coronavirus><Coronavirus Infections><Coronavirus glycoprotein S><Coronavirus spike protein><Disease Outbreaks><EV-68><EV-D68><Elements><Emerging Communicable Diseases><Emerging Infectious Diseases><Enterovirus 68><Enterovirus D68><Epitopes><Evaluation><Human><Hybrids><Immunity><Immunize><MERS corona virus><MERS coronavirus><MERS virus><MERS-CoV><Mice><Mice Mammals><Middle East Respiratory Syndrome Corona Virus><Middle East Respiratory Syndrome Coronavirus><Middle East Respiratory Syndrome Virus><Middle East Respiratory Syndrome-CoV><Middle East Respiratory coronavirus><Middle Eastern Respiratory Syndrome Corona virus><Middle Eastern Respiratory Syndrome Coronavirus><Middle Eastern Respiratory Syndrome Virus><Middle Eastern Respiratory Syndrome-CoV><Modern Man><Modification><Molecular Interaction><Monoclonal Antibodies><Murine><Mus><NIAID><National Institute of Allergy and Infectious Disease><Outbreaks><Protein Subunits><Proteins><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 vaccine><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2><SARS-CoV2 vaccine><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Subunit Vaccines><Testing><Vaccine Design><Vaccines><Variant><Variation><Viral><Viral load measurement><Virus><Virus-like particle><Wuhan coronavirus><beta CoV><beta coronavirus><betaCoV><betacoronavirus><corona virus><corona virus disease 2019><corona virus disease 2019 vaccine><coronavirus S protein><coronavirus disease 2019><coronavirus disease 2019 vaccine><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 vaccine><coronavirus disease-19 virus><coronavirus infectious disease-19><coronavirus spike glycoprotein><coronavirus vaccine><design><designing><develop a vaccine><develop vaccines><development of a vaccine><hCoV19><hybrid protein><immunogen><immunogenic><improved><kids><mAbs><model of animal><monoclonal Abs><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nCoV2><neutralizing antibody><particle><pathogen><plasmid DNA><pre-clinical><preclinical><respiratory><screening><screenings><severe acute respiratory syndrome coronavirus 2 variant><severe acute respiratory syndrome coronavirus 2 variant forms><severe acute respiratory syndrome coronavirus 2 variant strains><vaccine against 2019-nCov><vaccine against SARS-CoV-2><vaccine against SARS-CoV2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine against coronavirus><vaccine candidate><vaccine development><vaccine for novel coronavirus><vaccine platform><virology><virus load><virus-like nanoparticles><viruslike particle><youngster><β CoV><β coronavirus><βCoV>