University of Maryland, Baltimore

A participant must meet all the following criteria to be eligible for the study: - Adults ages 18 years and older. - Judged by the investigator to be healthy based on participant-reported medical history, physical examination, vital signs, and laboratory assessment. - Able to provide written informed consent. - Willing to disclose prior COVID-19 vaccination status. - Willing to disclose prior participant-reported SARS-CoV-2 infection status. - Prior receipt of at least 3 injections with a COVID-19 mRNA vaccine with the most recent dose at least 6 months prior to enrollment. - Willing to comply with all study procedures during the follow-up period of approximately 12 or 24 months, depending on number of doses received. - Body mass index of ≤ 40 kg/m2 within 30 days prior to enrollment - Electrocardiogram (ECG) without clinically significant abnormalities. Laboratory Criteria within 30 days before enrollment - White blood cells (WBC) and differential within institutional normal range or accompanied by the site Principal Investigator (PI) or designee approval. - Total lymphocyte count ≥ 800 cells/µL. - Platelets between 125,000 and 500,000 cells/µL. - Hemoglobin within institutional normal range or accompanied by the PI or designee approval. - Alanine aminotransferase (ALT) ≤ 1.25 x institutional upper limit of normal (ULN). - Aspartate aminotransferase (AST) ≤ 1.25 x institutional ULN. - Serum creatinine ≤ 1.1 x institutional ULN. - Ferritin, iron and TIBC within institutional normal range or accompanied by the PI or designee approval. For participants of childbearing potential: - Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test (urine or serum) on the day of enrollment. - Must agree to avoid pregnancy from 21 days prior to study Day 1 until at least 90 days after last study vaccination.

A participant will be excluded if one or more of the following conditions apply: - Known SARS-CoV-2 infection or positive test result within 6 months prior to Day 1. - Ongoing prophylactic COVID-19 treatment, or monoclonal antibody infusion within 6 months prior to Day 1. - Any COVID-19 vaccination within 6 months prior to Day 1. - Exhibits symptoms consistent with COVID-19 as assessed by study clinician such as: fever, dry cough, fatigue, nasal obstruction, runny nose, sore throat, myalgia, diarrhea, shortness of breath or dyspnea within 14 days prior to in Day 1. - Known close contact (as defined by CDC, 2021a) with someone who has COVID-19 within 14 days prior to Day 1. - History or presence of self-reported or medically documented significant medical or psychiatric condition(s) as assessed by study clinician, including: - At high risk of severe COVID-19 disease, such as significant history of COPD or chronic lung disease, chronic kidney disease, serious heart conditions (such as heart failure, coronary artery disease or cardiomyopathies), sickle cell disease, diabetes. - Clinically significant central nervous system disease such as epilepsy, encephalopathy, or a history of severe mental illness. - Severe liver and/or kidney diseases, uncontrolled hypertension, or ongoing or highly likely to recur malignancies. - Ongoing or recent clinically significant history of alcohol or drug abuse. - Current participation in an interventional clinical study with an investigational drug/biologic/device agent or receipt of any investigational agent within 30 days prior to Day 1. - Evidence of infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus. - History of myocarditis or pericarditis. - Diagnosed with congenital or acquired immune deficiency, ongoing lymphoma, leukemia, or other clinically significant immune compromising or autoimmune conditions. - History of known coagulation dysfunction (e.g., coagulation factor deficiency, known thrombocytopenia, platelet dysfunction, coagulation disease, etc.). - Receipt of any live attenuated vaccine within 30 days, or with any other (non-live) vaccine within 14 days prior to Day 1. - Received more than 10 days of any systemic immunosuppressants or cytotoxic medications within 30 days prior to Day 1, any within 14 days prior to Day 1 or is anticipating the need for immunosuppressants at any time during participation in the study. - Received any blood products within 3 months prior to Day 1. - Donated > 450 mL of whole blood within 30 days prior to Day 1. - History of unexplained or recurrent anaphylaxis or angioedema, or a history of severe allergic reaction (e.g., anaphylaxis) after a previous dose of any vaccine, or to any component of the study vaccine. - For participants of childbearing potential: breastfeeding or planning to become pregnant during trial duration. - Any condition that, in the opinion of the investigator, would (a) pose a health risk to the participant if enrolled or (b) could interfere with evaluation of the study vaccine or interpretation of study results.