Abstract
Coronavirus disease 2019 (COVID-19) continues to be a global health concern, and booster doses are necessary for maintaining vaccine-mediated protection, limiting the spread of severe acute respiratory syndrome coronavirus 2. Despite multiple COVID-19 vaccine options, global booster uptake remains low. Reactogenicity, the occurrence of adverse local/systemic side effects, plays a crucial role in vaccine uptake and acceptance, particularly for booster doses. We conducted a targeted review of the reactogenicity of authorized/approved messenger RNA (mRNA) and protein-based vaccines demonstrated by clinical trials and real-world evidence. It was found that mRNA-based boosters show a higher incidence and an increased severity of reactogenicity compared with the Novavax protein-based COVID-19 vaccine (NVX-CoV2373). In a recent study from the National Institute of Allergy and Infectious Diseases, the incidence of pain/tenderness, swelling, erythema, fatigue/malaise, headache, muscle pain, or fever was higher in individuals boosted with BNT162b2 (0.4% to 41.6% absolute increase) or mRNA-1273 (5.5% to 55.0% absolute increase) compared with NVX-CoV2373. Evidence suggests that NVX-CoV2373, when utilized as a heterologous booster, demonstrates less reactogenicity compared with mRNA vaccines, which, if communicated to hesitant individuals, may strengthen booster uptake rates worldwide. Clinical Trials Registration NCT04889209.