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 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 30,000 participants will take part in the study. Following authorization for Emergency Use in the US based on demonstration of statistically significant vaccine efficacy and satisfactory safety in an analysis of the primary endpoint sufficient to support the application for EUA, 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.