Safety and Immunogenicity Trial of an Oral SARS-CoV-2 Vaccine (VXA-CoV2-1) for Prevention of COVID-19 in Healthy Adults and Boost (VXA-CoV2-1.1-S) at 1 Year Post Initial Vaccination in Subset of Subjects

This is an open-label, dose-ranging trial to determine the safety and immunogenicity of an orally administered adenoviral-vector based vaccine (VXA-COV2-1) expressing a SARS-CoV-2 antigen and dsRNA adjuvant. Post screening activities, healthy adult volunteers aged 18 - 54 yrs old, inclusive, will be enrolled into the study. Participants will receive an oral dose of vaccine at Days 1 and a subject will also receive a second dose at Day 29; total study period will last ~ 2 months during the active phase, with a total 12 month safety follow-up period post last vaccination. Safety, reactogenicity and immunogenicity assessments will be performed at set times during the study active and follow-up periods. Subjects will be monitored for symptoms of COVID-19 throughout the duration of the study follow-up period.

Approximately 10 healthy male and female adult volunteers 18 to 54 years old who were enrolled in the main study will be included in a boost extension substudy for an additional 12 months from dosing for a total participation period of 24-25 months.

Inclusion criteria

• Male or female between the ages of 18 to 54 years, inclusive.
• Negative for SARS-CoV-2 infection at the time of screening
• In generally good health, without significant medical illness
• Demonstrates comprehension of the protocol procedures and is able to provide written informed consent.
• Available for all planned visits and willing to complete all protocol defined procedures and assessments
• Body mass index between 17 and 30 kg/m2 at screening.
• Female subjects must have a negative pregnancy test at screening and before each vaccination and fulfill an acceptable method of birth control (per protocol)

Exclusion criteria

• Known previous exposure to SARS-CoV-2 or receipt of an investigational product for the prevention or treatment of COVID-19, middle east respiratory syndrome (MERS), or severe acute respiratory syndrome (SARS).
• Is in a current occupation with high risk of exposure to SARS-CoV-2
• Individuals with the following underlying medical conditions who are at higher risk (or might be at higher risk) of severe illness from COVID-19 per the CDC's guidance
• Donation or use of blood or blood products within 4 weeks prior to vaccination or planned donation during the study period.
• Diagnosed bleeding disorder or significant bruising or bleeding difficulties that could make blood draws problematic.
• Any condition that resulted in the absence or removal of the spleen.
• Positive HIV, HBsAg or HCV tests at the screening visit.
• Stool sample with occult blood at screening.
• Use of antiviral medications, including anti-retrovirals, or any prescriptive medications for the prevention of COVID-19 within 7 days before vaccination
• Use of antibiotics, proton pump inhibitors, H2 blockers or antacids or medications known to affect the immune function within 7 to 14 days before vaccination
• Regular use of nonsteroidal anti-inflammatory drugs, sulfonylureas, and angiotensin II blockers within 7 days before vaccination
• Acute disease within 72 hours prior to vaccination defined as the presence of a moderate or severe illness
• History of drug, alcohol or chemical abuse within 1 year of screening or positive urine drug screen for drugs of abuse at screening
• History of hypersensitivity or allergic reaction to any component of the investigational vaccine
• Administration of any investigational vaccine, drug or device within 8 weeks preceding vaccination
• Any other condition that in the clinical judgment of the investigator would jeopardize the safety or rights of a subject participating in the trial, would render the subject unable to comply with the protocol or would interfere with the evaluation of the study endpoints.

For subjects being re-evaluated for participation in the VXA-CoV2-1.1-S boost substudy the following will also be exclusionary:

• Laboratory values outside the range of normal for platelet counts and the following coagulation tests: PT/INR, aPTT, fibrinogen, and D-dimer.
• Any of the following history or conditions that may lead to higher risk of clotting events and/or thrombocytopenia:

e. Family or personal history of bleeding or thrombosis f. History of heparin-related thrombotic events, and/or receiving heparin treatments g. History of autoimmune or inflammatory disease h. Presence of any of the following conditions known to increase risk of thrombosis within 6 months prior to screening:

• Recent surgery other than removal/biopsy of cutaneous lesions
• Immobility (confined to bed or wheelchair for 3 or more successive days)
• Head trauma with loss of consciousness or documented brain injury
• Receipt of anticoagulants for prophylaxis of thrombosis
• Recent clinically significant infection