Hawaii Biotech COVID-19 Response to PA-18-591

7. Project Summary/Abstract Coronaviruses have been identified in several avian hosts, as well as in various mammals, includingcamels, 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 3significant coronavirus outbreaks that have greatly impacted global health. First, there was the SevereAcute 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 causesin referred to as COVID-19. On March 11, 2020, as a result of the rapid global spread of the virus, the WHOdeclared that COVID-19 had reached pandemic levels. The emergence of the novel SARS-CoV-2necessitates the need to develop effective medical counter measures to effectively respond to the publichealth threat posed by this virus. Currently, there are at least 40 SARS-CoV-2 vaccine candidates indevelopment. These employ methods that include nucleic acid-based vaccines, viral vectored vaccines, VLPbased vaccines, and recombinant subunit vaccines. Our approach to develop a SARS-CoV-2 vaccine is touse an Administrate Supplement to the current SBIR Phase IIB grant (2R44AI118017-03), "Cross-ProtectiveMultivalent Vaccine for Tick-Borne Flaviviruses." The overall goal of this administrative supplement isto expand the scope of the current grant and leverage the use of the S2 cell vaccine platform toexpress recombinant subunits representing the SARS-CoV-2 spike protein and determine theirpotential 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 ofimmune responses elicited by the SARS-CoV-2 recombinant subunits will include novel adjuvantformulations 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 atransgenic mouse model. In the development of coronavirus vaccines, it is important to carefully evaluatevaccine candidates in terms of safety as prior studies have identified concerns of enhanced disease as aresult of skewed antibody responses that result in inflammatory alveolar damage. Our studies are designedto address these concerns through the design of subunits and the use of adjuvants that engender balancedTh1/Th2, or Th1 biased responses. The proposed recombinant subunit approach provides a means todeliver a safe, stable, and established manufacturing platform for a SARS CoV-2 vaccine.