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Principal Investigator: TREVOR P. CASTOR
Organization: APHIOS CORPORATION
Fiscal Year: 2023
Award: $300,000
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY
COVID-19, the multiorgan disease caused by the novel coronavirus SARS-CoV-2, has become the most
impactful healthcare, social, and economic crisis of our lifetime. SARS-CoV-2 is genetically related to the
previous two coronaviruses that caused human outbreaks in the 21st century, SARS-CoV and MERS-CoV. Even
though COVID-19 mortality is lower than the other two coronavirus diseases, the pandemic has impacted, by
mid-April 2022, >500 million people worldwide, and caused >6 million deaths. Had the COVID-19 mortality been
closer to those of SARS and MERS, the impact of the current pandemic would be incomparably more
catastrophic. The need for cold storage, the requirement for boosters, and the potential for adverse allergic
reactions, are major drawbacks of current COVID-19 vaccines.
To address these shortcomings, we propose to generate a COVID-19 mRNA vaccine that is stable at room
temperature, requires only one injection, thus being more practical to deploy nationally and globally during
vaccination campaigns, and is less prone to cause hypersensitivity reactions. We plan to conduct this Proof-of-
Concept study over a 24-month period with a multidisciplinary team of engineers, molecular virologists, and
immunologists. Our overarching goal is to double nanoencapsulate the mRNA molecule that encodes the
coronavirus Spike protein in phospholipid nanosomes and then into biodegradable polymer nanospheres to
sustain mRNA release. We will characterize the antigenicity and integrity of the nanoencapsulated mRNA before
and after nanoencapsulation and coating and determine the best process conditions that ensure stability at room
temperature after lyophilization. We will also evaluate the safety, pharmacokinetics, and immunogenicity of the
nanoencapsulated antigen and perform challenge studies in two animal models, in anticipation of subsequent
clinical studies. Based on these studies, we will select the best nanoformulation for scale-up, more detailed
characterization, establish potency and release specifications, and regulatory studies in Phase II.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><Acute><Address><Allergic Reaction><Allergy><Animal Model><Animal Models and Related Studies><Antigens><Biologic Sciences><Biological Sciences><Bioscience><COVID><COVID infected patient><COVID patient><COVID positive patient><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 infected patient><COVID-19 mortality><COVID-19 patient><COVID-19 positive patient><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 mortality><COVID19 patient><COVID19 positive patient><COVID19 related death><COVID19 related fatality><COVID19 related mortality><COVID19 vaccine><COVID19 virus><CV-19><CV19><Cessation of life><Clinical Research><Clinical Study><CoV S protein><CoV disease><CoV emergence><CoV glycoprotein S><CoV pandemic><CoV spike glycoprotein><CoV spike protein><CoV-2><CoV2><Communicable Diseases><Coronaviridae><Coronavirus><Coronavirus glycoprotein S><Coronavirus spike protein><Country><Cryofixation><Cryopreservation><Death><Development><Disease><Disease Outbreaks><Disorder><Dose><Drug Kinetics><Economics><Education><Educational aspects><Encapsulated><Engineering><Ensure><European Community><European Union><Fatality rate><Freeze Drying><Freeze Dryings><Future><GS-5734><Gene Proteins><Goals><Government><Healthcare><Human><Hypersensitivity><Immunologist><Impoverished><In Vitro><Individual><Industry><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Injections><Life><Life Expectancy><Life Sciences><Lipids><Liquid substance><Lyophilization><MERS><MERS corona virus><MERS coronavirus><MERS coronavirus disease><MERS virus><MERS-CoV><MERS-CoV disease><Macrogols><Measures><Mental Health><Mental Hygiene><Messenger RNA><Middle East Respiratory Syndrome><Middle East Respiratory Syndrome CoV disease><Middle East Respiratory Syndrome Corona Virus><Middle East Respiratory Syndrome Coronavirus><Middle East Respiratory Syndrome Virus><Middle East Respiratory Syndrome coronavirus disease><Middle East Respiratory Syndrome-CoV><Middle East Respiratory coronavirus><Middle Eastern Respiratory Syndrome><Middle Eastern Respiratory Syndrome CoV disease><Middle Eastern Respiratory Syndrome Corona virus><Middle Eastern Respiratory Syndrome Coronavirus><Middle Eastern Respiratory Syndrome Virus><Middle Eastern Respiratory Syndrome coronavirus disease><Middle Eastern Respiratory Syndrome-CoV><Minority><Modern Man><Modification><Molecular><Nanosphere><Organ><Outbreaks><Persons><Pharmacokinetics><Phase><Phosphatides><Phospholipids><Physical distancing><Polyethylene Glycols><Polyethylene Oxide><Polyethyleneoxide><Polymers><Polyoxyethylenes><Poverty><Preventative strategy><Prevention strategy><Preventive strategy><Process><Protein Gene Products><Psychological Health><RNA vaccine><RNA-based vaccine><Race><Races><Reaction><Reporting><Resolution><SARS><SARS Virus><SARS corona virus><SARS corona virus 2><SARS coronavirus><SARS coronavirus disease><SARS-Associated Coronavirus><SARS-CO-V2><SARS-COVID-2><SARS-CoV><SARS-CoV disease><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 infected patient><SARS-CoV-2 mortality><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 related death><SARS-CoV-2 related fatality><SARS-CoV-2 related mortality><SARS-CoV-2 vaccine><SARS-CoV2><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><Safety><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><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe Acute Respiratory Syndrome CoV disease><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe Acute Respiratory Syndrome coronavirus disease><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><Social Distance><Societies><Solvents><Specific qualifier value><Specified><Technology><Temperature><Therapeutic><Universities><Vaccination><Vaccines><Veklury><Viral><Viral Vector><Virus><Wuhan coronavirus><biodegradable polymer><biological systems><bioresorbable polymer><cold preservation><cold storage><corona virus><corona virus disease><corona virus disease 2019><corona virus disease 2019 vaccine><corona virus emergence><coronavirus S protein><coronavirus disease><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 infected patient><coronavirus disease 2019 mortality><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><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 infected patient><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease-19><coronavirus disease-19 mortality><coronavirus disease-19 patient><coronavirus disease-19 vaccine><coronavirus disease-19 virus><coronavirus emergence><coronavirus infectious disease-19><coronavirus pandemic><coronavirus patient><coronavirus spike glycoprotein><current pandemic><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><degradable polymer><developmental><economic><emergent CoV><emergent corona virus><emergent coronavirus><emerging CoV><emerging corona virus><emerging coronavirus><face mask><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><fluid><future pandemic><hCoV19><health care><immunogen><immunogenicity><in vivo><in vivo evaluation><in vivo testing><innovate><innovation><innovative><liquid><mRNA><mRNA Stability><mRNA vaccine><mRNA-based vaccine><manufacturability><model of animal><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 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2><pill><polymer><polymeric><pre-pandemic><present pandemic><racial><racial background><racial origin><reconstitute><reconstitution><remdesivir><resolutions><scale up><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 infected patient><severe acute respiratory syndrome coronavirus 2 mortality><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><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><socio-economic><socio-economically><socioeconomically><socioeconomics><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 for novel coronavirus><vector-based vaccine>