A Phase 2b, Randomized, Double-blind, Active-controlled Study of Single Dose CVXGA Intranasal COVID-19 Vaccine in Adults

Inclusion Criteria:

• Is an adult ≥18 years of age at time of screening.

• Has completed any WHO/FDA-authorized or approved primary COVID-19 vaccinationseries.

• Has received last COVID-19 vaccine no less than 6 months prior to study enrollment (study vaccination).

• If a female of childbearing potential who is sexually active, agrees to use anadequate method of birth control from Screening through 90 days after last studyvaccination, and has used an adequate birth control method for at least 30 daysprior to Screening.

A. Female of childbearing potential is defined as post onset menarche and pre-menopausal person capable of becoming pregnant. This does not include females who meet any of the following conditions: a) menopausal >2 years; b) tubal ligation >1 year; c) bilateral salpingo-oophorectomy; or d) hysterectomy.

B. Adequate contraception is defined as a contraceptive method with a failure rate of less than 1% per year when used consistently and correctly and when applicable, in accordance with the product label. Examples include: oral contraceptives, either combined or progestogen alone; injectable progestogen; implants of etonogestrel or levonorgestrel; estrogenic vaginal ring; percutaneous contraceptive patches; intrauterine device or intrauterine system; the female participant has exclusively female sexual partners; partner is sterile or otherwise unable to produce sperm (information on the person's sterility can come from the site personnel's review of the participant's medical records or interview with the participant regarding her medical history); male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository); or male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository).

• Is medically stable, as determined by the site investigator (based on review ofhealth status, vital signs, medical history, and physical examination).

• Agrees to not participate in any other SARS-CoV-2 infection prevention trial (vaccine, drug, biologic, or pre-exposure prophylaxis [PrEP]) during participationin the study.

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

• Is available for all study visits, willing to participate in all study procedures,and not planning to relocate from the area for the duration of the study.

Exclusion Criteria:

• Has an acute illness, as determined by the site investigator, within 72 hours priorto Screening or study vaccination.

(a. An acute illness that is nearly resolved, with only minor residual symptomsremaining, is allowable if, in the opinion of the site investigator, the residualsymptoms will not interfere with the ability of study staff to assess safetyparameters as required by the protocol.)

• Has had a positive COVID-19 test within the 90 days prior to Screening or studyvaccination.

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

• Prior receipt of a PIV5-based vaccine (e.g., CVXGA1, CVXGA35, or BLB201 [an RSVvaccine being developed by CyanVac/Blue Lake Biotechnology]).

• Participation in research involving any investigational product within 45 days priorto Screening or study vaccination.

• Receipt of any approved or authorized products intended to prevent SARS-CoV-2infection within 6 months prior to Screening (complete list provided in the pharmacymanual).

• Receipt or anticipated receipt of, within 7 days prior through 31 days after studyvaccination, any intranasal medication including FDA approved prescription orover-the-counter products or non-FDA approved alternative medicine products (e.g.,intranasal Fluticasone {commonly used intranasal products that would be used, whichis not herbal/naturopathic}, Ayurvedic oil or other naturopathic substances).

• Anticipated use of nasal irrigation (e.g., Neti PotTM) from Screening through 31days after study vaccination.

• Receipt of blood products or immunoglobulins within 60 days prior to Screening orstudy vaccination.

• Received influenza vaccination within 14 days prior to Screening or studyvaccination, or any other vaccine within 30 days prior to Screening or studyvaccination.

• Any significant or uncontrolled autoimmune, immunodeficiency disease/condition, orautoinflammatory disorder (e.g. untreated or advanced human immunodeficiency virus [HIV] infection with CD4 counts <200 cells/mm3, history of acquired immunodeficiencysyndrome [AIDS] defining illness without immune reconstitution, or clinicalmanifestations of symptomatic HIV).

• Unstable illness (acute or chronic illness) requiring significant medical monitoringand intervention during the 90 days prior to Screening or study vaccination.

• History of myocarditis, pericarditis, or idiopathic cardiomyopathy, or presence ofany medical condition that, in the opinion of the investigator, increases risk ofmyocarditis or pericarditis.

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

1. B-cell therapies within the 6 months prior to Screening or study vaccination.

2. Prednisone, ≥20 mg for more than 2 weeks, within the 30 days prior to Screeningor study vaccination.

3. Monoclonal antibodies that may suppress aspects of immune response (e.g.,Dupixent) within the 6 months prior to Screening or study vaccination.

4. 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 Screening or study vaccination.

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

• Individuals who have close contact or high-risk contact with persons who may beseverely immunocompromised, within 14 days following the study vaccination.High-risk contacts include but are not limited to:

1. Residents of nursing homes or rehabilitation facilities

2. Persons of any age with any significant immunodeficiency disease (e.g.,untreated or advanced HIV, history of AIDS, or clinical manifestations of HIV)

3. Persons of any age being administered immunosuppressants, systemicglucocorticoids, or other immune-modifying drugs

4. Persons of any age with a known history of significant airway reactivity toviruses (e.g., severe asthma, advanced chronic obstructive disease, or cysticfibrosis)

5. Persons of any age immunosuppressed due to cancer or undergoing activetreatment for cancer

6. Women who are pregnant, breastfeeding, or who plan to become pregnant duringthe study; and

7. Infants age ≤6 months.

• Known contraindication to IM injection (e.g., bleeding diathesis, acquiredcoagulopathy) or to intranasal administration (e.g., severe nasal obstruction,significant chronic rhinitis, nasal septal defect causing significant breathingproblems, unrepaired cleft palate, nasal polyps, or other nasal abnormality that, inthe opinion of the investigator, may affect vaccine administration).

• History of significant/severe wheezing or respiratory symptoms resulting inhospitalization or known bronchial hyperreactivity to viruses.

• History of severe adverse reaction to vaccination in the past, including to COVID-19vaccination.

• Any known allergies to components contained in CVXGA or COMIRNATY (includingpolyethylene glycol [PEG] allergies), or latex.

• Women who are pregnant, breastfeeding, or who plan to become pregnant during thestudy.

• Any other condition that, in the opinion of the site investigator, would pose ahealth risk to the participant if enrolled or could interfere with evaluation of theinvestigational product or interpretation of study results.

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