The purpose of this study is to investigate the immunogenicity and safety of mRNA COVID-19 variant-containing vaccine formulations against the vaccine-matched variants and newly emerged variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

This study uses a master protocol with a generic study design to allow flexibility in evaluating immunogenicity of variant-containing formulations of the mRNA-1273 COVID-19 vaccine. As different variant-containing vaccine formulations will be evaluated, each study intervention will be described in the subprotocol. For each evaluation of an updated variant vaccine or age group, a new subprotocol will be generated. Reported outcome measures are based upon master protocol. Not all reported outcome measures may be applicable to each subprotocol.

Key Inclusion Criteria:

• mRNA-1273.167 and mRNA-1273.712: Previously vaccinated adults aged ≥18 years

• mRNA-1273.251: Participants ≥65 years of age, ≥12 to <65 years of age, or ≥6 months to <12 years of age with at least 1 risk factor for severe outcomes from COVID-19.

• mRNA-1273.261: ≥65 years of age at the time of signing the informed consent or ≥18 to <65 years of age at the time of signing the informed consent with at least 1 risk factor for severe outcomes from COVID-19.

• Able to comply with study procedures based on the assessment of the Investigator.

• Female participants of childbearing potential may be enrolled in the study if the participant fulfills all the following criteria:

  • Has a negative pregnancy test at the Screening Visit and on the day of vaccination prior to vaccine dose being administered on Day 1.
  • Has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first dose.
  • Has agreed to continue adequate contraception through 28 days following vaccine administration.

Key Exclusion Criteria:

• History of SARS-CoV-2 infection within 3 months prior to enrollment for mRNA-1273.167 and mRNA-1273.712 or within up to 6 months prior to enrollment for mRNA-1273.251 and mRNA-1273.261.
• Is acutely ill or febrile (temperature 38.0°Celsius/100.4°Fahrenheit) less than 72 hours prior to or at the Screening Visit or Day 1. Participants meeting this criterion may be rescheduled within the Screening window.
• History of a diagnosis or condition that, in the judgment of the Investigator, is clinically unstable, or may affect participant safety, assessment of study endpoints, assessment of immune response, or adherence to study procedures.
• History of anaphylaxis or severe hypersensitivity reaction requiring medical intervention after receipt of any mRNA vaccine or therapeutic or any components of an mRNA vaccine or therapeutic.
• Receipt of COVID-19 vaccine within 3 months prior to enrollment for mRNA-1273.167 and mRNA-1273.712 or within 6 months prior to enrollment for mRNA-1273.251 and mRNA-1273.261.
• Receipt of any licensed non-COVID-19 vaccine within 14 days (inactivated vaccine, pediatric) or 28 days before or planned receipt within 14 days (pediatric) or 28 days after the study intervention, except an influenza vaccine, which may be given at least 7 days before (pediatric) or 14 days before or after receipt of the study intervention.
• Receipt of systemic immunosuppressants or immune-modifying drugs for >14 days total (within 6 months prior to Screening for mRNA-1273.167 and mRNA-1273.712 or within 180 days prior to Screening for mRNA-1273.251 and mRNA-1273.261) or is anticipating the need for immunosuppressive treatment at any time during participation in the study.
• Receipt of systemic immunoglobulins, long-acting biological therapies that affect immune (pediatric) responses, or blood products (within 3 months prior to Screening for mRNA-1273.167 and mRNA-1273.712 or within 90 days prior to the Screening for mRNA-1273.251 and mRNA-1273.261) or plans for receipt during the study.
• Has donated ≥450 milliliters of blood products within 28 days prior to the Screening Visit or plans to donate blood products during the study.

Other protocol-defined inclusion/exclusion criteria may apply.