A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults

Inclusion Criteria: 1. Provides written informed consent before initiation of any study procedures. 2. Able to understand and agree to comply with planned study procedures and be available for all study visits. 3. Non-pregnant adults, 18 through 64 years of age at the time of study product administration. 4. Participants of childbearing potential\* must agree to use or have practiced true abstinence\*\* or use at least one acceptable primary form of contraception.\*\*\* \*These criteria apply to females who are in a heterosexual relationship and are of childbearing potential. Not of childbearing potential include post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, or tubal ligation/salpingectomy). \*\*True abstinence is 100 percent of the time, no sexual intercourse (penis enters the vagina). Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods. \*\*\*Acceptable forms of primary contraception include a monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more before the participant's study product administration, a copper intrauterine device, a levonorgestrel-releasing intrauterine device, a progestin-only oral contraceptive pill, a depot medroxyprogesterone injection, or a progestin implant. Combined hormonal contraceptives containing estrogen, including combined oral contraceptive pills, transdermal patches, and vaginal rings, are not acceptable for this trial. Must have used at least one acceptable primary form of contraception for at least 30 days before study product administration and agree to continue at least one acceptable primary form of contraception through 60 days after study product administration. 5. Participants of childbearing potential must have a negative urine pregnancy test at screening and within 24 hours before study product administration. 6. In general, good health.\* \*As determined by medical history and physical examination, including vital signs, to evaluate acute or ongoing chronic medical diagnoses/conditions that have been present for at least 90 days, which would affect the assessment of participant safety. Chronic medical diagnoses/ conditions should be stable for the last 30 days (i.e., no hospitalization, ER, or urgent care for the condition). This includes no change in chronic prescription medication, dose, or frequency due to deterioration of the chronic medical diagnosis or condition within the 30 days preceding the study product administration. Any prescription change that is due to a change of health care provider, insurance company, etc., or done for financial reasons, and in the same class of medication, will not be considered a deviation of this inclusion criterion. Participants may be on chronic or as-needed (prn) medications if, in the opinion of the participating site PI or appropriate sub-investigator, they pose no additional risk to participant safety or assessment of reactogenicity and immunogenicity. 7. Receipt of a complete primary COVID-19 vaccine series and at least one booster\* with last vaccination at least 16 weeks before study product administration. \*Booster may be either homologous or heterologous to the primary vaccine series. It must be an FDA-authorized/licensed vaccine, though doses may have been received as part of a clinical trial. 8. Clinical screening laboratory evaluations are within normal reference ranges or grade 1 with no clinical significance (NCS) per investigator discretion.\* \*(White Blood Cells \[WBCs\] with differential \[diff\], hemoglobin \[Hgb\], platelets \[PLTs\], PTT, PT, Alanine Transaminase \[ALT\], Aspartate Transaminase \[AST\], Creatinine \[Cr\], Alkaline Phosphatase \[ALP\], Total Bilirubin \[T. Bili\]). ALT, AST, ALP, T. Bili, and creatinine values that are below the reference range will not be exclusionary, as these values below the reference range are clinically insignificant. 9. Must agree to have samples stored for secondary research. 10. Must complete a Test of Understanding (ToU) before enrollment by answering 90 percent of questions correctly at least once in 3 attempts. Exclusion Criteria: 1. Positive SARS-CoV-2 PCR at screening. 2. Abnormal vital signs (Grade 1 or higher).\* \*Grade 1 or higher is equivalent to: Systolic blood pressure (SBP) = 141 mmHg or = 89 mmHg Diastolic blood pressure (DBP) = 91 mmHg Heart rate (HR) is = 101 beats per minute or = 54 beats per minute Oral temperature = 38.0 degrees Celsius (100.4 degrees Fahrenheit) 3. History of SARS-CoV-2 infection within the prior 16 weeks OR receipt of any COVID-19 vaccine within the prior 16 weeks before study product administration. 4. Participant who is pregnant or breastfeeding or less than 12 weeks post partum at the time of study product administration. 5. Participant has donated blood or plasma within 4 weeks prior to study product administration, or does not agree to refrain from blood or plasma donation until Day 181. 6. Receipt of antibody or blood-derived products within 90 days before study product administration. 7. Any significant medical or psychiatric diseases or any other condition that, in the opinion of the site PI or appropriate sub-investigator, precludes study participation.\* \*Significant self-reported or medically reported medical or psychiatric conditions include, but are not limited to drug or alcohol abuse within 6 months of enrollment, significant kidney disease, liver disease, history of hematologic malignancies, ongoing malignancy or recent diagnosis of malignancy in the last five years, excluding treated basal cell and squamous cell carcinoma of the skin, and cervical carcinoma in situ, which are allowed. 8. Any respiratory disease, including but not limited to chronic obstructive pulmonary disease (COPD), asthma, interstitial lung disease, bronchiectasis, etc. 9. Neurological or neurodevelopmental conditions.\* \*These conditions include: history of Bell's palsy, history of four or more migraine headaches in the past 12 months that interfered with normal daily activity or any migraine headache in the past 5 years that required emergency or inpatient medical care, epilepsy, seizures in the last 5 years, encephalopathy, focal neurologic deficits, Guillain-Barré syndrome, myelopathy, peripheral neuropathy, encephalomyelitis, transverse myelitis, stroke or transient ischemic attack, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, or Alzheimer's disease. 10. Cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease), including any history of myocarditis or pericarditis, or uncontrolled cardiac arrhythmia. 11. Any autoimmune disease, including hypothyroidism without a defined non-autoimmune cause. 12. Any significant nasal or upper airway disease.\* \*Including, but not limited to, being prone to epistaxis, a history of inflammatory rhinitis (including allergic rhinitis) that requires daily medications, cochlear implants, head/neck radiation history, anosmia/dysosmia, conditions that require prescription or over the counter intranasal medication (intermittent use will be allowed if no use occurred for 30 days before study product administration and participant agrees to not use intranasal medication (other than steroids) for 30 days after study product administration and to not use intranasal steroids for 6 months after study product administration), and certain ear, nose and throat (ENT) conditions, including significant upper airway/nasopharyngeal disease or abnormal anatomy such as CSF leak. 13. Has an acute illness, as determined by the site Principal Investigator or appropriate sub-investigator within 72 hours before study product administration.\* \*An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the participating site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol. 14. Has a positive test result for hepatitis B surface antigen, hepatitis C virus RNA (by reflex testing), or human immunodeficiency virus (HIV) antigen/antibody test at screening. 15. Has any confirmed or suspected immunosuppressive or immunodeficient state, such as asplenia, recurrent severe infections, and chronic\* immunosuppressant medication within the past 6 months.\*\* \*Chronic meaning more than 14 continuous days. \*\*Ophthalmic and topical steroids are allowed, see exclusions 12 and 21 for intranasal steroids. 16. Has received any investigational product within 60 days, or 5 half-lives, whichever is longer, before study product administration; or is planning to receive one during the study. 17. Has a history of hypersensitivity or severe allergic reaction\* to any previous licensed or unlicensed vaccine or to the candidate vaccine components. \*e.g., anaphylaxis, generalized urticaria, angioedema, other significant reaction 18. History of chronic idiopathic urticaria. 19. Received or plans to receive licensed inactivated/subunit vaccine within 14 days of study product administration or live vaccine within 28 days of study product administration. 20. Plan to receive a COVID-19 vaccine within the 180 days following study product administration. 21. Regular use of intranasal medications, including steroids.\* \*Participant must have had no intranasal medication use for 30 days before study product administration and plans not to use intranasal medications for 30 days after study product administration for medications other than steroids, and for 6 months after study product administration for intranasal steroids (including over-the-counter fluticasone). 22. History of smoking within three months before enrollment.\* \*Including cigarettes, smokeless and other tobacco products, e-cigarettes (to include vaping and Juuling products), marijuana, nicotine gum, and nicotine lozenges. 23. Use of intranasal illicit drugs in the 5 years before study product administration or plans to use during the study. 24. Planned international travel between study product administration and Day 29. 25. Previous receipt of any adenovirus-vector vaccine by the intranasal or aerosol routes. 26. Bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following Intramuscular injections or venipuncture. 27. Recent (within 3 months of study product administration): major surgery, \>=3 days immobility, chronic infection, or head trauma that may increase thrombosis risk.\* \*Major surgery is either abdominal or vascular, or orthopedic surgery, and immobility implies bed rest. 28. History of venous or arterial thrombosis or any known thrombophilic condition, including heparin-induced thrombocytopenia (HIT) or thrombosis. 29. BMI \>/= 40kg/m\^2 30. Current/planned systemic estrogen therapy, except stable transdermal estradiol, from 30 days pre-dose through end of study participation. Low-dose vaginal estrogen is permitted.