This is a Phase 3 study to evaluate the effectiveness, immune response, and safety of a coronavirus disease 2019 (COVID-19) vaccine called SARS-CoV-2 rS with Matrix-M1 adjuvant in adults 18 years of age and older with a pediatric expansion in adolescents (12 to 17 years) in the United States and Mexico.

A vaccine causes the body to have an immune response that may help prevent the infection or reduce the severity of symptoms. An adjuvant is something that can make a vaccine work better. This study will look at the protective effect, body's immune response, and safety of SARS-CoV-2 rS with Matrix-M1 adjuvant in the study population.

Participants in the study will randomly be assigned to receive SARS-CoV-2 rS with Matrix-M1 adjuvant or placebo. Each participant in the study will receive a total of 2 intramuscular injections of either ARS-CoV-2 rS with Matrix-M1 adjuvant or placebo in the Initial Vaccination Period. Up to 33,000 participants will take part in the study.

Following the recommendation of COVID-19 vaccination for all adults 18 years of age and older, adult participants will be scheduled for the administration of 2 injections of the alternate study material 21 days apart ("blinded crossover").

That is, initial recipients of placebo will receive SARS-CoV-2 rS with Matrix-M1 adjuvant and initial recipients of SARS-CoV-2 rS with Matrix-M1 adjuvant will receive placebo. A blinded crossover will be implemented for adolescents 12-17 years of age approximately 6 months after the initial vaccination.