Evaluation of the Safety and Immunogenicity of a SARS-CoV-2 rS (COVID-19) Nanoparticle Vaccine With/Without Matrix-M Adjuvant

Inclusion Criteria (Phase 1):

• Healthy adult males or females between 18 and 59 years of age, inclusive, at screening (Phase 1). Healthy status will be determined by the investigator based on medical history, clinical laboratory results, vital sign measurements, and physical examination at screening.
• The subject has a body mass index 17 to 40 kg/m2, inclusive, at screening.
• Willing and able to give informed consent prior to study enrollment and comply with study procedures.
• Female subjects of childbearing potential (defined as any female who has experienced menarche and who is NOT surgically sterile [ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy] or postmenopausal [defined as amenorrhea at least 12 consecutive months or documented plasma follicle-stimulating hormone level ≥40 mIU/mL]) must agree to be heterosexually inactive from at least 21 days prior to enrollment and through 6 months after the last vaccination OR agree to consistently use any of the described methods of contraception from at least 21 days prior to enrollment and through 6 months after the last vaccination.

Exclusion Criteria (Phase 1):

• Any ongoing, symptomatic acute or chronic illness requiring medical or surgical care, inclusive of changes in medication in the past 2 months indicating that chronic illness/disease is not stable (at the discretion of the investigator). This includes any current workup of undiagnosed illness that could lead to a new condition.
• Chronic disease inclusive of: a) hypertension uncontrolled for age according to JNC 8 guidelines; b) congestive heart failure by NYHA functional classification of greater or equal to II; c) chronic obstructive pulmonary disease by GOLD classification of greater or equal to 2; d) recent (within 6 months prior to first study vaccination) exacerbation of coronary artery disease as manifested by cardiac intervention, addition of new cardiac medications for control of symptoms, or unstable angina; e) asthma (diagnosed by spirometry showing reversibility of disease and must meet at least the Step 1 classification with current prescription/use of medications to control symptoms); f) diabetes requiring use of medicine (insulin or oral) or not controlled with diet.
• Participation in research involving an investigational product (drug/biologic/device) within 45 days prior to first study vaccination.
• History of a confirmed diagnosis of SARS or COVID-19 disease (confirmed by a specific test for each disease) or known exposure to a SARS-CoV-2 positive confirmed close contact (eg, family member, housemate, daycare provider, aged parent requiring care), at the discretion of the investigator.
• Currently working in an occupation with a high risk of exposure to SARS-CoV-2 (eg, healthcare worker, emergency response personnel).
• Currently taking any product (investigational or off-label) for prevention of COVID-19 disease.
• Positive rapid test for SARS-CoV-2 (ELISA or PCR) at screening or prior to first vaccination (if available).
• Received influenza vaccination within 14 days prior to first study vaccination, or any other vaccine within 4 weeks prior to first study vaccination.
• Any autoimmune or immunodeficiency disease/condition (iatrogenic or congenital).
• Chronic administration (defined as more than 14 continuous days) of immunosuppressant, systemic glucocorticosteroids, or other immune-modifying drugs within 4 months prior to first study vaccination or anticipation of the need for immunosuppressive treatment within 6 months after last vaccination.
• Received immunoglobulin, blood-derived products, or other immunosuppressant drugs within 90 days prior to first study vaccination.
• Any acute illness concurrent or within 14 days prior to first study vaccination (medical history and/or physical examination) or documented temperature of >38°C during this period. This includes respiratory or constitutional symptoms consistent with SARS-CoV-2 (COVID-19) exposure (ie, cough, sore throat, difficulty breathing)
• Known disturbance of coagulation (iatrogenic or congenital). NOTE: The use of ≤325 mg of aspirin per day as prophylaxis is permitted, but the use of other platelet aggregation inhibitors, thrombin inhibitors, Factor Xa inhibitors, or warfarin derivatives is exclusionary, regardless of bleeding history, because these imply treatment or prophylaxis of known cardiac or vascular disease.
• Evidence of Hepatitis B or C or HIV by laboratory testing.
• A positive test result for drugs of abuse (except a positive test result associated with prescription medication that has been reviewed and approved by the investigator) or alcohol at screening.
• Any neurological disease or history of significant neurological disorder (eg, meningitis, seizures, multiple sclerosis, vasculitis, migraines, Guillain-Barré syndrome [genetic/congenital or acquired]).
• Active cancer (malignancy) within 5 years prior to first study vaccination (with the exception of adequately treated non-melanomatous skin carcinoma, at the discretion of the investigator)
• Vital sign (blood pressure, pulse, temperature) abnormalities of toxicity grade >1
• Clinical laboratory abnormalities of toxicity grade >1 for selected serum chemistry and hematology parameters
• Any known allergies to products contained in the investigational product or latex allergy.
• Women who are pregnant, breastfeeding or who plan to become pregnant during the study.
• History of alcohol abuse or drug addiction within one year prior to the first study vaccination.
• Any condition that, in the opinion of the investigator, would pose a health risk to the subject if enrolled or could interfere with evaluation of the study vaccine or interpretation of study results (including neurologic or psychiatric conditions deemed likely to impair the quality of safety reporting).
• Study team member or first-degree relative of any study team member (inclusive of sponsor, PPD, and site personnel involved in the study).