Document text
Principal Investigator: Daniel Kulp
Organization: WISTAR INSTITUTE
Fiscal Year: 2022
Award: $2,626,814
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary
In December 2019 a novel coronavirus, named sudden acute respiratory syndrome coronavirus-2 (SARS-CoV-
2). SARS-CoV-2 rapidly spread around the globe causing a pandemic disease termed coronavirus disease of
2019 (COVID-19). There have been more than 80 million infections and close to two million deaths from COVID-
19 to date. SARS-CoV-2 is the third beta coronavirus of zoonotic origin to cause human epidemics. It is similar
to, but distinct from, Middle East respiratory syndrome coronavirus (MERS-CoV) and sudden acute respiratory
syndrome virus-1 (SARS-CoV-1), both of which have caused outbreaks this century. While several candidate
vaccines for SARS-CoV-2 have recently received emergency use authorization, the longevity of vaccine-induced
responses, the continued emergency of mutation within SARS-CoV-2 strains, and the disproportionate morbidity
and mortality among elderly patient populations present continued challenges to control of SARS-CoV-2. Thus,
vaccine modalities which can address these challenges for SARS-CoV-2 vaccines and allow for targeting of
multiple potentially pandemic coronaviruses simultaneously are greatly needed. Innovative vaccines which
can develop broad immunity against known and newly emergent human coronavirus is a key goal in the
field. The effects of antigen epitope diversity, density, valency, duration of antigen availability, and adjuvant-
induced cytokine environment on the potency and breadth of vaccine-induced Reponses remains unclear.
Nanoparticle vaccine formulations allow the ability to manipulate these variables. We have generated self-
assembling synthetic DNA-launched nanoparticle vaccines (DLNPs) which displayed increased immunogenicity
compared to matched synthetic DNA launched monomer vaccines or protein-in-adjuvant formulations. We
determined that synthetic DNA launched nanoparticles increased both cellular and humoral responses.
Recombinant nanoparticle vaccines are thought to mediate their increased immunogenicity by persisting in the
lymph nodes for extended periods compared to protein antigens, promoting enhanced antigen presentation by
follicular dendritic cells and increasing germinal center formation and humoral immunity. Cell-mediated
responses to nanoparticle vaccines are less well understood but similar mechanisms may be at play. We will
capitalize on the novel in vivo assembling synDLNP platform we have created to manipulate these variables and
determine their effects on acute and long-term responses to CoV antigens in young and aged models.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><ACE2><Acute><Address><Adjuvant><Airway mucosa><Animal Model><Animal Models and Related Studies><Animals><Antibody Repertoire><Antigen Presentation><Antigenic Determinants><Antigens><Automobile Driving><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Bats><Binding Determinants><Binding Sites><COVID-19><COVID-19 associated death><COVID-19 associated fatality><COVID-19 associated mortality><COVID-19 death><COVID-19 fatality><COVID-19 induced death><COVID-19 induced fatality><COVID-19 induced mortality><COVID-19 infection><COVID-19 mortality><COVID-19 related death><COVID-19 related fatality><COVID-19 related mortality><COVID-19 vaccine><COVID-19 virus><COVID19><COVID19 associated death><COVID19 associated fatality><COVID19 associated mortality><COVID19 death><COVID19 fatality><COVID19 induced death><COVID19 induced fatality><COVID19 induced mortality><COVID19 infection><COVID19 mortality><COVID19 related death><COVID19 related fatality><COVID19 related mortality><COVID19 vaccine><COVID19 virus><CV-19><CV19><Cell Body><Cells><Chiroptera><CoV emergence><CoV-2><CoV2><Combination Vaccines><Combined Vaccines><Combining Site><Coronaviridae><Coronaviridae Infections><Coronavirus><Coronavirus Infections><DNA><Deoxyribonucleic Acid><Development><Disease Outbreaks><Dose><Emergencies><Emergency Situation><Engineering><Environment><Epidemic><Epitopes><Event><FDA EUA><FDA Emergency Use Authorization><Family><Family member><Follicular Dendritic Cells><Food and Drug Administration EUA><Food and Drug Administration Emergency Use Authorization><Formulation><Genetic><Genetic Alteration><Genetic Change><Genetic defect><Germinal Center><Goals><HCoV><Human><Humoral Immunities><Immune memory><Immune response><Immunity><Immunization><Immunochemical Immunologic><Immunologic><Immunologic Memory><Immunologic Sensitization><Immunologic Stimulation><Immunological><Immunological Memory><Immunological Sensitization><Immunological Stimulation><Immunological response><Immunologically><Immunologics><Immunostimulation><In Vitro><Infection><Kinetics><Length of Life><Longevity><Lymph Node Reticuloendothelial System><Lymph node proper><Lymphatic nodes><MERS corona virus><MERS coronavirus><MERS virus><MERS-CoV><Mediating><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 Eastern Respiratory Syndrome Corona virus><Middle Eastern Respiratory Syndrome Coronavirus><Middle Eastern Respiratory Syndrome Virus><Middle Eastern Respiratory Syndrome-CoV><Modality><Modeling><Modern Man><Molecular><Morbidity><Morbidity - disease rate><Mucosa><Mucosal Tissue><Mucous Membrane><Murine><Mus><Mutation><Names><Nucleic Acids><Outbreaks><Peripheral><Play><Point Mutation><Population><Production><Proteins><Publishing><Reactive Site><Receptor Protein><Recombinants><Respiratory Mucosa><Role><SARS Virus><SARS corona virus><SARS corona virus 2><SARS coronavirus><SARS-Associated Coronavirus><SARS-CO-V2><SARS-COVID-2><SARS-CoV><SARS-CoV-1><SARS-CoV-2><SARS-CoV-2 associated death><SARS-CoV-2 associated fatality><SARS-CoV-2 associated mortality><SARS-CoV-2 death><SARS-CoV-2 fatality><SARS-CoV-2 induced death><SARS-CoV-2 induced fatality><SARS-CoV-2 induced mortality><SARS-CoV-2 infection><SARS-CoV-2 mortality><SARS-CoV-2 related death><SARS-CoV-2 related fatality><SARS-CoV-2 related mortality><SARS-CoV-2 vaccine><SARS-CoV2><SARS-CoV2 infection><SARS-CoV2 vaccine><SARS-Related Coronavirus><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><Serotyping><Severe Acute Respiratory Coronavirus><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 Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><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 corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Structure><Structure of germinal center of lymph node><Surface><Syndrome><T cell response><T-Cells><T-Lymphocyte><Transmission><Vaccines><Viral Diseases><Virus><Virus Diseases><Wild Type Mouse><Wuhan coronavirus><Zoonoses><Zoonotic><Zoonotic Infection><aged><anamnestic reaction><angiotensin converting enzyme 2><angiotensin converting enzyme II><antibody-based immunity><base><beta CoV><beta coronavirus><betaCoV><betacoronavirus><clinical relevance><clinically relevant><corona virus><corona virus disease 2019><corona virus disease 2019 vaccine><corona virus emergence><coronavirus disease 2019><coronavirus disease 2019 associated death><coronavirus disease 2019 associated fatality><coronavirus disease 2019 associated mortality><coronavirus disease 2019 death><coronavirus disease 2019 fatality><coronavirus disease 2019 induced death><coronavirus disease 2019 induced fatality><coronavirus disease 2019 induced mortality><coronavirus disease 2019 infection><coronavirus disease 2019 mortality><coronavirus disease 2019 related death><coronavirus disease 2019 related fatality><coronavirus disease 2019 related mortality><coronavirus disease 2019 vaccine><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 mortality><coronavirus disease-19 vaccine><coronavirus disease-19 virus><coronavirus emergence><coronavirus infectious disease-19><coronavirus of pandemic concern><coronavirus of pandemic potential><coronavirus receptor><coronavirus vaccine><coronavirus with pandemic potential><cytokine><death due to COVID-19><death due to COVID19><death due to SARS-CoV-2><death due to coronavirus disease 2019><death due to severe acute respiratory syndrome coronavirus 2><death in COVID><death in COVID-19><death in SARS-CoV-2><death in coronavirus disease><death in coronavirus disease 2019><death in severe acute respiratory syndrome coronavirus 2><density><design><designing><develop a vaccine><develop vaccines><development of a vaccine><developmental><driving><elderly patient><emergency use authorization><emergent CoV><emergent corona virus><emergent coronavirus><emerging CoV><emerging corona virus><emerging coronavirus><fatality due to COVID-19><fatality due to COVID19><fatality due to SARS-CoV-2><fatality due to coronavirus disease 2019><fatality due to severe acute respiratory syndrome coronavirus 2><genome mutation><hCoV19><host response><human CoV><human corona virus><human coronavirus><immune system response><immunogen><immunogenic><immunogenicity><immunoresponse><in vivo><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><innovate><innovation><innovative><life span><lifespan><lymph gland><lymph nodes><lymphnodes><model of animal><model organism><monomer><mortality><mortality due to COVID-19><mortality due to COVID19><mortality due to SARS-CoV-2><mortality due to coronavirus disease 2019><mortality due to severe acute respiratory syndrome coronavirus 2><nCoV><nCoV2><nano particle><nano particle delivery><nano vaccine><nano-sized particle><nanoparticle><nanoparticle delivered><nanoparticle delivery><nanosized particle><nanovaccine><new CoV><new corona virus><new coronavirus><next generation><novel><novel CoV><novel corona virus><novel coronavirus><older patient><pan CoV vaccine><pan coronavirus vaccine><panCoV vaccine><pancoronavirus vaccine><pandemic><pandemic coronavirus><pandemic disease><pandemic threat coronavirus><patient population><programs><receptor><respiratory><response><secondary immune response><severe acute respiratory syndrome coronavirus 2 associated death><severe acute respiratory syndrome coronavirus 2 associated fatality><severe acute respiratory syndrome coronavirus 2 associated mortality><severe acute respiratory syndrome coronavirus 2 death><severe acute respiratory syndrome coronavirus 2 fatality><severe acute respiratory syndrome coronavirus 2 induced death><severe acute respiratory syndrome coronavirus 2 induced fatality><severe acute respiratory syndrome coronavirus 2 induced mortality><severe acute respiratory syndrome coronavirus 2 mortality><severe acute respiratory syndrome coronavirus 2 related death><severe acute respiratory syndrome coronavirus 2 related fatality><severe acute respiratory syndrome coronavirus 2 related mortality><severe acute respiratory syndrome-CoV><social role><synthetic DNA><synthetic construct><thymus derived lymphocyte><transmission process><universal CoV vaccine><universal coronavirus vaccine><vaccination study><vaccination trial><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 formulation><vaccine response><vaccine responsiveness><vaccine study><vaccine trial><vaccine-induced immunity><vaccine-induced protection><vaccine-induced response><vaccinology><viral infection><virus infection><virus-induced disease><wildtype mouse><zoonotic CoV><zoonotic coronavirus><β CoV><β coronavirus><βCoV>