INCLUSION CRITERIA:  In order to be eligible to participate in this study, an individual must meet all of the following criteria:  Ability to provide informed consent. Stated willingness to comply with all study procedures (including discontinuing medications as needed and availability for the duration of the study. Aged 16-69 years. Must have experienced a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2 ng/mL] per modified CoFAR Grading Scale for Systemic Allergic Reactions Version 3.0) to the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine. Patients without documented hypoxia, hypotension, or evidence of end-organ damage who were treated with epinephrine infusion would be considered as CoFAR Grade 3 reaction and may be eligible per investigator discretion. Must be at least 28 days out from their first dose of the Moderna vaccine or 21 days from their first dose of the Pfizer-BioNTech vaccine before proceeding with the placebo or vaccine challenge in this study. Have a primary care physician or other health care provider who will manage their medical care outside of this study. Willing to allow storage of blood and other biological samples for future use in medical research.  EXCLUSION CRITERIA:  An individual who meets any of the following criteria will be excluded from participation in this study:  Experienced a Grade 4 systemic allergic reaction (per CoFAR Grading Scale for Systemic Allergic Reactions Version 3.0) to the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine. Known exposure to SARS-CoV-2 and still within the quarantine window. Symptoms consistent with acute COVID-19 infection or known COVID-19 infection (positive reverse transcription-polymerase chain reaction [RT-PCR] or antigen test) and still within the quarantine window Have an acute illness, including body temperature greater than 100.4 degrees F, within 14 days prior to enrollment. History of autoimmune or other disorders requiring systemic immune modulators. Are moderately or severely immunocompromised. History of acute urticaria within 28 days prior to enrollment. Pregnant. Have received any vaccines within 14 days prior to enrollment. Scheduled or planned receipt of approved or experimental vaccine prior to visit 3. Had any allergen immunotherapy administration within 24 hours prior to the first study vaccination or plan to receive within 24 hours after the second study vaccination. Have received a biological therapy within 6 months prior to enrollment. Use of systemic steroids for any reason within 28 days prior to enrollment. Use of zileuton within 14 days prior to enrollment. Use of EUA monoclonal antibodies casirivimab and indevimab, or bamlanivimab, or any other antibody agent for treatment or prevention of COVID-19 within 3 months of randomization. Presence of condition(s) that, in the judgment of the investigator or the referring physician, may put the participant at undue risk or make them unsuitable for participation in the study.