A Study to Evaluate VXA-CoV2-3.3 COVID-19 Vaccine Against Currently Approved/Authorized mRNA COVID-19 Injectable Booster Vaccine in Adults Previously Immunized Against COVID-19 Infection

Inclusion Criteria:

1. Adults 18 years of age and above, at time of screening.

2. Completed primary approved/authorized COVID-19 vaccination series with ≥ 2 mRNAvaccine doses.

3. Last COVID-19 vaccine received ≥6 months prior to study vaccination.

4. Male and female participants of childbearing potential must agree to consistentlyuse a highly effective method of contraception from at least 30 days prior toenrollment and through 3 months after the study vaccination.

5. Male participants must refrain from sperm donation from the day of study vaccinationthrough the end of the study. Female participants must refrain from egg donation atleast 30 days prior to study vaccination through the end of the study.

6. Is medically stable, as determined by the site investigator (based on review ofhealth status, vital signs, medical history, and physical examination) withscreening lab values within normal limits or abnormalities assessed as notclinically significant. Screening platelet count must be >140,000/μL.

7. Agree to not participate in any other SARS-CoV-2 infection prevention trial (vaccine, drug, biologic, PrEP) during participation in the study.

8. Willing and able to provide informed consent prior to initiation of studyprocedures.

9. Available for all study visits, willing to participate in all study procedures, andnot planning to relocate from the area for the duration of the study.

10. Negative rapid molecular Covid test at the screening visit and on Day 1 prior tovaccine dosing.

Exclusion Criteria:

1. Participant has an acute illness as defined by any of the following (note:assessment may be repeated once during screening period) as determined by the siteinvestigator, within 72 hours prior to vaccination as follows:

2. An acute illness that is nearly resolved, with only minor residual symptomsremaining, is allowable if, in the opinion of the site investigator, theresidual symptoms will not interfere with the ability of study staff to assesssafety parameters as required by the protocol.

3. Presence of a fever ≥ 38.0°C (100.4°F) measured orally at baseline, on Day 1prior to vaccination.

4. Receipt of antipyretic/analgesic medications within 24 hours prior to vaccineadministration.

5. Participant has had a positive COVID test within 90 days prior to screening.

6. Current or planned participation in any other interventional clinical trial.

7. Participation in research involving any investigational product within 45 days priorto study vaccination.

8. Receipt of any approved or authorized products intended to prevent SARS-CoV2infection within 6 months prior to study vaccination.

9. Receipt or donation of blood products or immunoglobulins within 60 days prior toenrollment or planned administration during the study.

10. Received influenza vaccination within 14 days prior to study vaccination, or anyother vaccine within 30 days prior to study vaccination.

11. Any autoimmune or immunodeficiency disease/condition (including and not limited tountreated or advanced HIV infection with CD4 counts <200 cells/mm^3, history of AIDSdefining illness without immune reconstitution, or clinical manifestations ofsymptomatic HIV, severe combined immunodeficiency (SCID), hypogammaglobulinemia,asplenia or functional asplenia).

12. Unstable medical or psychiatric illness (acute or chronic illness) requiringsignificant medical monitoring and intervention during the 90 days prior toenrollment. Note: diabetes mellitus (Types 1 & 2) are not excluded if assessed bythe principal investigator (PI) as well-controlled.

13. Administration of immunosuppressants, systemic glucocorticoids, or otherimmune-modifying drugs within the following timeframes:

14. B-cell therapies within the 6 months prior to first study vaccination

15. Prednisone, ≥20 mg for more than 2 weeks, within the 30 days prior to studyvaccination

16. Other medications in this category, including but not limited to high-doseinhaled corticosteroids (>800 mcg/day of beclomethasone dipropionate orequivalent); antimetabolites; transplant immunosuppressive agents; alkylatingagents; cell-depleting agents; or cancer chemotherapeutics, within the 90 daysprior to study vaccination.

17. Any medication for any period of time that, in the opinion of the siteinvestigator, could impede immune response to vaccination.

18. Use of any dose montelukast OR inhaled, intranasal, intra-articular, orsystemic corticosteroids within 2 weeks prior to study vaccination.

19. Planned use of any of the above medications during the study.

20. Concomitant allergen immunotherapy (AIT) will be allowed only if theparticipant is stable in the maintenance phase of AIT. Maintenance AIT shouldnot be dosed for at least 7 days before and 7 days after study vaccine dosing,and the PI must document the treating allergist's approval.

21. Known contraindication to IM injection or blood draws (e.g. bleeding diathesis,acquired coagulopathy, significant bleeding or bruising) or to oral route ofadministration (unable to swallow tablets).

22. Any known allergies to components contained in the investigational product orcomparator or latex allergy (including polyethylene glycol [PEG] allergies) and/orhistory of serious reactions to vaccination such as anaphylaxis, respiratoryproblems, hives, or abdominal pain.

23. Women who are pregnant (pregnancy tests will be performed at screening and prior todosing), breastfeeding, or who plan to become pregnant during the study.

24. History of irritable bowel disease or other inflammatory digestive orgastrointestinal condition that could affect the distribution/safety evaluation ofan orally administered vaccine targeting the mucosa of the small intestine. Suchconditions may include but are not limited to:

25. Any history of:

• GI malignancy
• malabsorption
• pancreatobiliary disorders
• inflammatory bowel disease
• irritable bowel disease
• hiatal hernia
• surgical resection

2. History of diagnosis or treatment in past 5 years of:

• esophageal or gastric motility disorder
• gastroesophageal reflux disorder
• peptic ulcer
• cholecystectomy.

15. Use of antibiotics, proton pump inhibitors, H2 blockers, or antacids within 7 daysprior to study drug administration or planned use from dosing through Day 31.

16. Use of drugs known to affect gastrointestinal motility including glucagon-likepeptide 1 (GLP-1) receptor agonists including tirzepatide (Mounjaro) and semaglutide (Wegovy, Ozempic) within 30 days prior to drug administration.

17. Daily use of nonsteroidal anti-inflammatory drugs within 7 days prior to study drugadministration or planned use during the study.

18. Personal or familial history of hypercoagulable states to include personal pasthistory of deep vein thrombosis (DVT).

19. Personal history of myocarditis or pericarditis.

20. Positive Hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody atthe screening visit.

21. History of drug, alcohol, or chemical abuse within 1 year of screening.

22. Positive urine drug screen for drugs of abuse at screening (except for occasionalmarijuana use). Concurrent or planned use of marijuana from dosing through Day 31 isprohibited. Positive urine drug screen (UDS) at screening due to prescribedstimulants will be reviewed on a case by case basis.

23. Cancer, or treatment for cancer, within the past 3 years (excluding fully treatedand resolved basal cell carcinoma or squamous cell carcinoma).

24. History of any form of angioedema.

25. History of GI bleeding including hematochezia (blood in stool) or melena (blackstool) of unknown etiology or that has not been evaluated.

26. Any history or conditions that may lead to a higher risk of clotting events and/orthrombocytopenia, including:

27. Familial coagulopathy or personal history of bleeding disorder or thrombosis

28. History of heparin-related thrombotic events, and/or receiving heparintreatments

29. History of autoimmune or inflammatory disease

30. Presence of any of the following conditions known to increase the risk ofthrombosis within 6 months prior to screening:

• Recent surgery other than fully healed cesarean delivery or excision/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 including hospitalization forCOVID-19 related illness.

27. Any other condition that, in the opinion of the investigator, would pose a healthrisk to the participant if enrolled or could interfere with evaluation of theinvestigational product or interpretation of study results.

28. Study team member or first-degree relative of any study team member (inclusive ofsponsor and site personnel involved in the study).