Safety and Immunogenicity Study of a SARS-CoV-2 (COVID-19) Variant Vaccine (mRNA-1273.351) in Naïve and Previously Vaccinated Adults

Inclusion Criteria: 1. Provides written informed consent prior to initiation of any study procedures. 2. Be able to understand and agrees to comply with planned study procedures and be available for all study visits. 3. Agrees to the collection of venous blood per protocol. 4. Cohort 1: previously received 2 doses of mRNA-1273 intramuscular (IM) as part of DMID 20-0003. 5. Cohort 1: Male or non-pregnant female, \>/= 18 years of age at time of enrollment. Cohort 2: Male or non-pregnant female, 18 through 55 years of age at time of enrollment. 6. Women of childbearing potential\* must agree to practice abstinence or use at least one acceptable primary form of contraception.\*\*, \*\*\* Note: These criteria are applicable to females in a heterosexual relationship and child-bearing potential (i.e., the criteria do not apply to subjects in a same sex relationship). \* Not of childbearing potential - 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, tubal ligation/salpingectomy, or Essure(R) placement). \*\* Acceptable forms of primary contraception include monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more prior to the subject's first vaccination, intrauterine devices, birth control pills, and injectable/implantable/insertable hormonal birth control products. \*\*\* Must use at least one acceptable primary form of contraception for at least 30 days prior to the first vaccination and at least one acceptable primary form of contraception for 60 days after the last vaccination. 7. In good health.\* \* As determined by medical history and physical examination to evaluate acute or ongoing chronic medical diagnoses/conditions that have been present for at least 90 days, which would affect the assessment of safety of subjects. Chronic medical diagnoses/conditions should be stable for the last 60 days (no hospitalizations, emergency room, or urgent care for condition or need for supplemental oxygen). This includes no change in chronic prescription medication, dose, or frequency as a result of deterioration of the chronic medical diagnosis/condition in the 60 days before enrollment. Any prescription change that is due to 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. Any change in prescription medication due to improvement of a disease outcome or for dose optimization, as determined by the participating site PI or appropriate sub-investigator, will not be considered a deviation of this inclusion criterion. Subjects 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 subject safety or assessment of reactogenicity and immunogenicity, and do not indicate a worsening of medical diagnosis/condition. Similarly, medication changes subsequent to enrollment and study vaccination are acceptable provided the change was not precipitated by deterioration in the chronic medical condition, and there is no anticipated additional risk to the subject or interference with the evaluation of responses to study vaccination. 8. Oral temperature is less than 100.0 degrees Fahrenheit (37.8 degrees Celsius). 9. Must agree to have samples stored for secondary research. 10. Agrees to adhere to Lifestyle Considerations throughout study duration. 11. Must agree to refrain from donating blood or plasma during the study (outside of this study). Exclusion Criteria: 1. Positive pregnancy test prior to each vaccine administration. 2. BMI \> 40.0 kg / m\^2. 3. Female subject who is breastfeeding. 4. Has any medical disease or condition that, in the opinion of the participating site PI or appropriate sub-investigator, precludes study participation.\* \* Including acute, subacute, intermittent or chronic medical disease or condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial. 5. Presence of self-reported or medically documented significant medical or psychiatric condition(s).\* \* Significant medical or psychiatric conditions include but are not limited to: Respiratory disease (e.g., chronic obstructive pulmonary disease \[COPD\], asthma) requiring daily medications currently or any treatment of respiratory disease exacerbations (e.g., asthma exacerbation) in the last 5 years. Asthma medications: inhaled, oral, or intravenous (IV) corticosteroids, leukotriene modifiers, long and short acting beta agonists, theophylline, ipratropium, biologics. Significant cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease), history of myocarditis or pericarditis as an adult, myocardial infarction (MI) within past 6 months, coronary artery bypass surgery or stent placement, or uncontrolled cardiac arrhythmia. Neurological or neurodevelopmental conditions (e.g., history of migraines in the past 5 years, epilepsy, stroke, seizures in the last 3 years, encephalopathy, focal neurologic deficits, Guillain-Barré syndrome, encephalomyelitis, transverse myelitis, stroke or transient ischemic attack, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, or Alzheimer's disease). Ongoing malignancy or recent diagnosis of malignancy in the last five years excluding basal cell and squamous cell carcinoma of the skin, which are allowed. An autoimmune disease, including hypothyroidism without a defined non-autoimmune cause, localized or history of psoriasis. An immunodeficiency of any cause. Chronic kidney disease, estimated glomerular filtration rate (eGFR) \< 60 mL / min / 1.73m\^2. Type 2 diabetes mellitus, not including prediabetes. 6. Has an acute illness\*, as determined by the participating site PI or appropriate sub-investigator, with or without fever \[oral temperature \>/= 38.0 degrees Celsius (100.4 degrees Fahrenheit)\] within 72 hours prior to each vaccination. \* 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. 7. Has participated in another investigational study involving any investigational product\* within 5 half-lives before the first vaccine administration. \* study drug, biologic or device. 8. Currently enrolled in or plans to participate in another clinical trial with an investigational agent\* that will be received during the study-reporting period.\*\* \* Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication. \*\* Up to 15 months after the first vaccination. 9. Has a history of hypersensitivity or severe allergic reaction (e.g., anaphylaxis, generalized urticaria, angioedema, other significant reaction) to drugs or any previous licensed or unlicensed vaccines or to polyethylene glycol (PEG) or a PEG-containing product. 10. Chronic use (more than 14 continuous days) of any medications that may be associated with impaired immune responsiveness.\* \* Including, but not limited to, systemic corticosteroids exceeding 10 mg/day of prednisone equivalent, allergy injections, immunoglobulin, interferon, immunomodulators, cytotoxic drugs, or other similar or toxic drugs during the preceding 6-month period prior to vaccine administration (Day 1). The use of low dose topical, ophthalmic, inhaled and intranasal steroid preparations will be permitted. 11. Anticipating the need for immunosuppressive treatment within the next 6 months. 12. Received immunoglobulins and/or any blood or blood products within the 4 months before the first vaccine administration or at any time during the study. 13. Has any blood dyscrasias or significant disorder of coagulation. 14. Received or plans to receive a licensed, live vaccine within 4 weeks before or after each vaccination. 15. Received or plans to receive a licensed, inactivated vaccine within 2 weeks before or after each vaccination. 16. Receipt of any other SARS-CoV-2 vaccine or any experimental coronavirus vaccine at any time prior to or during the study, except Cohort 1 subjects who received mRNA-1273 in DMID 20-0003. 17. Close contact of anyone known to have SARS-CoV-2 infection within 14 days prior to vaccine administration. 18. History of COVID-19 diagnosis, positive SARS-CoV-2 PCR test, or, for Cohort 2 only, a known positive SARS-CoV-2 serologic test. 19. On current treatment with investigational agents for prophylaxis of COVID-19.