To be included in this study, each individual must satisfy all of the following criteria: 1. Adults 18 to 49 years of age, inclusive, at screening 2. Willing and able to give informed consent prior to study enrollment and to comply with study procedures. 3. Participants of childbearing potential (defined as any participant who has experienced menarche and who is NOT surgically sterile [ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy] or postmenopausal [defined as amenorrhea at least 12 consecutive months]) must agree to be heterosexually inactive from at least 28 days prior to enrollment and through the end of study (EOS) visit OR agree to consistently use a medically acceptable method of contraception from at least 28 days prior to enrollment and through the EOS visit. 4. Is medically stable, as determined by the investigator (based on review of health status, vital signs [to include body temperature], medical history, and targeted physical examination [to include body weight]). Vital signs must be within medically acceptable ranges prior to the study vaccination 5. Agree to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study. Note: For participants who become hospitalized with coronavirus disease 2019 (COVID-19), participation in investigational treatment studies is permitted. 6. Documented receipt of either 2 or 3 doses of the investigational Novavax vaccine with Matrix-M adjuvant (NVX- CoV2373); OR documented receipt of a full course of an FDA-authorized/approved COVID-19 vaccine; OR documented receipt of a full course of heterologous COVID-19 vaccines mentioned above. The most recent dose must have been administered at least 6 months prior to study vaccination.

Participants meeting any of the following criteria will be excluded from the study. 1. History of laboratory-confirmed (by polymerase chain reaction [PCR] or rapid antigen test)COVID-19 infection ≤ 4 months prior to randomization. 2. Current participation in research involving receipt of an investigational product (drug/biologic/device). 3. Any known allergies or history of anaphylaxis to the active substance or any of the other ingredients contained in the investigational product. 4. Any autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) or therapy that causes clinically significant immunosuppression. 5. Received any vaccine ≤ 90 days prior to study vaccination, except for influenza vaccine which may be received 4 days prior to study vaccine, or rabies vaccine which may be received at any time if medically indicated. 6. Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to study vaccination, except for rabies immunoglobulin which may be given if medically indicated. 7. Active cancer (malignancy) on chemotherapy that is judged to cause significant immunocompromise within 1 year prior to first study vaccination (with the exception of malignancy cured via excision, at the discretion of the investigator). 8. Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the EOS visit. 9. Suspected or known history of alcohol abuse or drug addiction within 3 months prior to the study vaccine dose that, in the opinion of the investigator, might interfere with protocol compliance. 10. Any other condition that, in the opinion of the investigator, would pose a health risk to the participant if enrolled or could interfere with evaluation of the trial vaccine or interpretation of study results (including neurologic or psychiatric conditions likely to impair the quality of safety reporting). 11. Study team member or immediate family member of any study team member (inclusive of Sponsor, clinical research organization [CRO], and study site personnel involved in the conduct or planning of the study). 12. Participants with a history of myocarditis or pericarditis.