A Randomized Clinical Trial Investigating the Safety, Reactogenicity, and Immunogenicity After Immunization With an mRNA-based Mpox Vaccine Candidate in Africa

This is a randomized, double-blind, placebo-controlled study which aims to assess the safety, reactogenicity, and immunogenicity after one and two doses of BNT166a or placebo in healthy participants.

Key Inclusion Criteria (applicable to all participants unless otherwise specified): * Are male or female individuals ≥18 years of age at the time of giving informed consent: * Cohort 1: ≥18 to ≤45 years of age * Cohort 2: ≥18 to ≤64 years of age * Cohort 1: Participants must be Orthopoxvirus-naïve (have no history of smallpox or mpox vaccination or mpox infection). * Cohort 2: Participants must be Orthopoxvirus-experienced (have evidence of mpox or smallpox vaccination or mpox infection at least 2 years prior to consent). Key Exclusion Criteria (applicable to all participants unless otherwise specified): * Have had recent exposure to mpox (defined as close contact with a probable or confirmed case of mpox within the past 28 days, or have evidence of mpox infection or mpox vaccination within 2 years prior to consent). * Have a contraindication, warning and/or precaution to vaccination with a messenger ribonucleic acid (mRNA) Coronavirus disease 2019 (COVID-19) vaccine as specified in the Summary of Product Characteristics for BNT162b2 (COMIRNATY United States Prescribing Information/European Union Summary of Product Characteristics) and BNT166 Investigator Brochure. * Have a history of allergies, hypersensitivities, or intolerance to the study treatments including any excipients thereof. * Have a current or history of cardiovascular diseases, e.g., myocarditis, pericarditis, myocardial infarction, congestive heart failure, cardiomyopathy, or clinically significant arrhythmias. * Have any known bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection. * Have a body mass index ≤18.5 kg/m\^2 or ≥35 kg/m\^2. NOTE: Other protocol defined Inclusion/Exclusion criteria apply.