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Principal Investigator: DAVID E CLEMENTS
Organization: HAWAII BIOTECH, INC.
Fiscal Year: 2020
Award: $389,739
Funding agency: National Institute of Allergy and Infectious Diseases
7. Project Summary/Abstract
Coronaviruses have been identified in several avian hosts, as well as in various mammals, including
camels, bats, palm civets, mice, dogs, and cats. Among the coronaviruses that are pathogenic to humans,
most are associated with mild clinical symptoms. However, In the last 18 years there have now been 3
significant coronavirus outbreaks that have greatly impacted global health. First, there was the Severe
Acute Respiratory Syndrome (SARS) in 2002, then the Middle East Respiratory Syndrome (MERS) in 2012,
and most recently a novel coronavirus in 2019, now officially named SARS-CoV-2 and the disease it causes
in referred to as COVID-19. On March 11, 2020, as a result of the rapid global spread of the virus, the WHO
declared that COVID-19 had reached pandemic levels. The emergence of the novel SARS-CoV-2
necessitates the need to develop effective medical counter measures to effectively respond to the public
health threat posed by this virus. Currently, there are at least 40 SARS-CoV-2 vaccine candidates in
development. These employ methods that include nucleic acid-based vaccines, viral vectored vaccines, VLP
based vaccines, and recombinant subunit vaccines. Our approach to develop a SARS-CoV-2 vaccine is to
use an Administrate Supplement to the current SBIR Phase IIB grant (2R44AI118017-03), “Cross-Protective
Multivalent Vaccine for Tick-Borne Flaviviruses.” The overall goal of this administrative supplement is
to expand the scope of the current grant and leverage the use of the S2 cell vaccine platform to
express recombinant subunits representing the SARS-CoV-2 spike protein and determine their
potential as vaccine candidates. Subunits that represent the Spike (S) glycoprotein ectodomain
(transmembrane region removed) and the S RBD will be expressed with and without trimerization domains.
The biochemical and immunological characteristics of subunits will be determined. The evaluation of
immune responses elicited by the SARS-CoV-2 recombinant subunits will include novel adjuvant
formulations with different mechanisms of action in an effort to identify formulations that induce potent,
protective immune responses, and support dose sparing, while avoiding Th2 biases immune responses.
Formulations that provide the best immunogenic responses will be utilized to assess protective efficacy in a
transgenic mouse model. In the development of coronavirus vaccines, it is important to carefully evaluate
vaccine candidates in terms of safety as prior studies have identified concerns of enhanced disease as a
result of skewed antibody responses that result in inflammatory alveolar damage. Our studies are designed
to address these concerns through the design of subunits and the use of adjuvants that engender balanced
Th1/Th2, or Th1 biased responses. The proposed recombinant subunit approach provides a means to
deliver a safe, stable, and established manufacturing platform for a SARS CoV-2 vaccine.
Terms: <2019 novel coronavirus><2019-nCoV><AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Address><Adjuvant><Administrative Supplement><Alveolar><Angiotensin Converting Enzyme><Angiotensin I-Converting Enzyme><Animals><Antibody Response><Antigens><Antiviral Agents><Antiviral Drugs><Antivirals><Assay><Aves><Avian><Bats><Bioassay><Biochemical><Biologic Assays><Biological Assay><Biotech><Biotechnology><Birds><CD143 Antigens><COVID-19><COVID19><Camels><Canine Species><Canis familiaris><Carboxycathepsin><Cats><Cats Mammals><Cell Body><Cell Line><CellLine><Cells><Characteristics><China><Chiroptera><Civet Cats><Civets><Clinical><Clinical Trials><CoV S protein><CoV emergence><CoV glycoprotein S><CoV spike glycoprotein><CoV spike protein><Coronaviridae><Coronavirus><Coronavirus glycoprotein S><Coronavirus spike protein><Dengue><Development><Dipeptidyl Peptidase A><Disease><Disease Outbreaks><Disorder><Dogs><Dogs Mammals><Domestic Cats><Dose><Drosophila><Drosophila genus><Ebola><Egypt 101 virus><Envelope Protein><Evaluation><FUS-1 Protein><Family><Feline Species><Felis catus><Felis domestica><Felis domesticus><Felis sylvestris catus><Flaviviridae><Flavivirus><Formulation><Fusion 1 Protein><Genome><Glycoproteins><Goals><Grant><Grippe><Group B Arbovirus><HIV><Hawaii><Human><Human Immunodeficiency Viruses><Immune response><Immunochemical Immunologic><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Infection><Inflammatory><Influenza><Insecta><Insects><Insects Invertebrates><Kininase A><Kininase II><LAV-HTLV-III><Length><Lymphadenopathy-Associated Virus><MERS><MERS corona virus><MERS coronavirus><MERS coronavirus disease><MERS virus><MERS-CoV><MERS-CoV disease><Mainland China><Mammalia><Mammals><Measures><Mediating><Medical><Methods><Mice><Mice Mammals><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 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><Modeling><Modern Man><Murine><Mus><Names><Non-Polyadenylated RNA><Nuclear Envelope><Nuclear Membrane><Nucleic Acids><Outbreaks><PDGFA associated protein 2><Pathogenicity><Patients><Peptides><Peptidyl-Dipeptidase A><Phase><Process><Production><Property><Protein Subunits><Proteins><Province><Public Health><RNA><RNA Gene Products><Receptor Protein><Recombinant Proteins><Recombinants><Research><Ribonucleic Acid><SARS><SARS Virus><SARS corona virus><SARS coronavirus><SARS coronavirus disease><SARS-Associated Coronavirus><SARS-CoV><SARS-CoV disease><SARS-CoV-2><SARS-CoV2><SARS-Related Coronavirus><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><SBIR><Safety><Sales><Saudi Arabia><Sea-Food><Seafood><Severe Acute Respiratory Syndrome><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 coronavirus 2><Small Business Innovation Research><Small Business Innovation Research Grant><Standardization><Strains Cell Lines><Structural Protein><Structure><Subunit Vaccines><Symptoms><System><TM Domain><Technology><Texas><Tick-Borne Encephalitis><Tick-borne Viral Encephalitis><Transgenic Mice><Transmembrane Domain><Transmembrane Region><Universities><Vaccines><Viral><Viral Pneumonia><Viral Vector><Virus><Virus-HIV><Viverridae><WNV><West Nile><West Nile virus><Work><Wuhan coronavirus><anti-viral agents><anti-viral drugs><anti-virals><base><canine><corona virus><corona virus disease 2019><coronavirus S protein><coronavirus disease 2019><coronavirus emergence><coronavirus spike glycoprotein><cultured cell line><design><designing><develop a vaccine><development of a vaccine><developmental><domestic dog><drug development><emergent CoV><emergent coronavirus><emerging CoV><emerging coronavirus><env Antigens><env Gene Products><env Polyproteins><env Protein><experience><flu infection><fruit fly><global health><host response><immunogen><immunogenic><immunoresponse><influenza infection><member><mouse model><murine model><nCoV><neutralizing antibody><new CoV><new coronavirus><new vaccines><next generation vaccines><novel><novel CoV><novel coronavirus><novel vaccines><pandemic><pandemic disease><plasmid vaccine><pre-clinical development><preclinical development><priority pathogen><protective efficacy><receptor><receptor binding><receptor bound><response><severe acute respiratory syndrome-CoV><tick-borne><tickborne><tickborne encephalitis><tickborne viral encephalitis><vaccine candidate><vaccine development><vaccine formulation><vector vaccine>