This trial protocol outlines a Phase 1/2, placebo-controlled, randomized, observer-blind, dose-finding study to evaluate the safety, tolerability, immunogenicity, and potential efficacy of four RNA-based SARS-CoV-2 vaccine candidates against COVID-19 in healthy adults. The study involves three stages: Stage 1 aims to identify preferred vaccine candidates, dose levels, and schedules; Stage 2 expands the cohort; and Stage 3 conducts a large-scale evaluation. The four vaccine candidates are BNT162a1, BNT162b1, BNT162b2, and BNT162c2, each based on different RNA platforms (unmodified mRNA, nucleoside-modified mRNA, and self-amplifying mRNA) and encoding different antigens. Participants are aged 18-55, 65-85, or 18-85 years, with stratification based on age. The study includes 15 participants per group in Stage 1, with up to 840 participants in total. Stage 2 involves 225 participants per group, and Stage 3 includes 3000 participants. The study will monitor adverse events, immunogenicity, and safety, with data monitored by an internal review committee and an external data monitoring committee. The primary objective is to assess safety and immunogenicity, while secondary objectives include efficacy. The study is designed to rapidly develop and evaluate vaccines against SARS-CoV-2, with the potential for dose escalation and candidate selection based on safety and immunogenicity data. Participants must be healthy, with no pre-existing conditions that would contraindicate participation. The study includes detailed procedures for vaccine administration, safety assessments, and follow-up visits. The protocol also includes measures to ensure participant confidentiality and compliance with regulatory requirements.This trial protocol outlines a Phase 1/2, placebo-controlled, randomized, observer-blind, dose-finding study to evaluate the safety, tolerability, immunogenicity, and potential efficacy of four RNA-based SARS-CoV-2 vaccine candidates against COVID-19 in healthy adults. The study involves three stages: Stage 1 aims to identify preferred vaccine candidates, dose levels, and schedules; Stage 2 expands the cohort; and Stage 3 conducts a large-scale evaluation. The four vaccine candidates are BNT162a1, BNT162b1, BNT162b2, and BNT162c2, each based on different RNA platforms (unmodified mRNA, nucleoside-modified mRNA, and self-amplifying mRNA) and encoding different antigens. Participants are aged 18-55, 65-85, or 18-85 years, with stratification based on age. The study includes 15 participants per group in Stage 1, with up to 840 participants in total. Stage 2 involves 225 participants per group, and Stage 3 includes 3000 participants. The study will monitor adverse events, immunogenicity, and safety, with data monitored by an internal review committee and an external data monitoring committee. The primary objective is to assess safety and immunogenicity, while secondary objectives include efficacy. The study is designed to rapidly develop and evaluate vaccines against SARS-CoV-2, with the potential for dose escalation and candidate selection based on safety and immunogenicity data. Participants must be healthy, with no pre-existing conditions that would contraindicate participation. The study includes detailed procedures for vaccine administration, safety assessments, and follow-up visits. The protocol also includes measures to ensure participant confidentiality and compliance with regulatory requirements.