Inclusion Criteria:

1. Is an adult 18 through 64 years of age at time of screening with at least 1
underlying condition that puts the participant at high risk for severe outcomes of
COVID-19 per self-report OR is an adult ≥65 years of age at time of screening (with
or without at least 1 underlying condition).

2. Has completed any WHO/FDA-authorized or approved primary COVID-19 vaccination series
per self-report.

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

4. If a female of childbearing potential who is sexually active, agrees to use an
adequate method of birth control from Screening through 90 days after study
vaccination, and has used an adequate birth control method for at least 30 days
prior to Screening. Sexually active male participants, unless the participant is
sterile or otherwise unable to produce sperm, or has exclusively male sexual
partners, must agree to abstinence or to use a barrier method (e.g., male condom)
from vaccination through 90 days after study vaccination. Male participants must
also agree to not donate sperm from vaccination through 90 days after study
vaccination.

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

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

7. Willing and able to provide informed consent prior to initiation of study
procedures.

8. 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:

1. Has an acute illness, as determined by the site investigator, within 72 hours prior
to Screening or study vaccination.

2. Has had a positive COVID-19 test within the 90 days prior to Screening or study
vaccination.

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

4. Participation in research involving any investigational product within 45 days prior
to Screening or study vaccination.

5. Receipt of any approved or authorized products intended to prevent SARS-CoV-2
infection within 6 months prior to Screening or study vaccination.

6. Receipt of blood products or immunoglobulins within 60 days prior to Screening or
study vaccination.

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

8. Any significant autoimmune, immunodeficiency disease/condition, or auto inflammatory
disorder (e.g., any known immunoglobulin A [IgA] deficiency, human immunodeficiency
virus [HIV] infection, acquired immunodeficiency syndrome [AIDS])

9. Has current active hepatitis B or hepatitis C infection (based on self-reported
medical history).

10. Has a peripheral arterial oxygen saturation (SpO2) level <92% at Screening,
uncontrolled or severe asthma (e.g., more than 1 hospitalization for asthma
exacerbation within the 12 months prior to Screening), or other uncontrolled or
severe chronic lung disease or known bronchial hyper-reactivity to viruses that, in
the opinion of the site investigator, would pose a health risk to the individual if
enrolled.

11. Has known active tuberculosis.

12. Unstable non-cardiac illness (acute or chronic illness) requiring hospitalization or
medical procedure during the 90 days prior to Screening or study vaccination, or
cardiac condition (acute or chronic) requiring hospitalization or medical procedure
(e.g., stenting, cardiac surgery, etc.) during the 1 year prior to Screening or
study vaccination.

13. History of myocarditis, pericarditis, myopericarditis, or idiopathic cardiomyopathy,
or presence of any medical condition (e.g., viral illness within 30 days of
Screening or study vaccination) that, in the opinion of the investigator, increases
risk of myocarditis, pericarditis, or myopericarditis.

14. Chronic kidney disease requiring dialysis or any type of ultrafiltration.
Individuals with chronic kidney disease that does not require dialysis or
ultrafiltration may be included.

15. Individuals with advanced or decompensated chronic liver disease as determined by
the site investigator.

16. Presence of any transplanted solid organs (heart, kidney, lung, liver, pancreas,
and/or intestine) or prior receipt of a blood stem cell transplant.

17. Administration of immunosuppressants, systemic glucocorticoids, or other
immune-modifying drugs within the following timeframes:

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

2. Prednisone, ≥20 mg or equivalent for more than 2 weeks, within the 30 days
prior to Screening or 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-dose
inhaled corticosteroids (>800 mcg/day of beclomethasone dipropionate or
equivalent); antimetabolites; transplant immunosuppressive agents; alkylating
agents; cell-depleting agents; or cancer chemotherapeutics, within the 90 days
prior to Screening or study vaccination.

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

18. Known contraindication to IM injection (e.g., bleeding diathesis, acquired
coagulopathy) or to IN administration (e.g., significant nasal abnormality or severe
nasal obstruction, significant chronic rhinitis or history of chronic rhinitis,
nasal septal defect causing significant breathing problems, unrepaired cleft palate,
nasal polyps, or other nasal abnormality that might affect vaccine administration).

19. Receipt or anticipated receipt, within 7 days prior through 7 days after study
vaccination, of any Intranasal medication, including FDA-approved prescription or
over-the-counter products or non-FDA-approved alternative medicine products (e.g.,
Ayurvedic oil or other naturopathic substances).

20. Anticipated use of nasal irrigation (e.g., Neti PotTM) from Screening through 30
days after study vaccination.

21. Any known allergies to components contained in NDV-HXP-S (including egg products) or
the comparator vaccine (including polyethylene glycol [PEG] allergies).

22. Women who are pregnant, breastfeeding, or who plan to become pregnant during the
study.

23. Current or prior potential for NDV exposure (e.g., prior NDV-based vaccination,
NDV-based oncologic immunotherapy, prior or current experience as a bird-handler,
poultry farmer, or scientist conducting research with NDV).

24. Individuals who will have close or household high-risk contacts, within 14 days
following study vaccination, including but not limited to:

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

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