evidence: Since the discovery of messenger RNA (mRNA), there have been tremendous efforts to wield them in the development of therapeutics and vaccines. During the COVID-19 pandemic, two mRNA vaccines were developed and approved in record-breaking time, revolutionizing the vaccine development landscape. Although first-generation COVID-19 mRNA vaccines have demonstrated over 90% efficacy, alongside strong immunogenicity in humoral and cell-mediated immune responses, their durability has lagged compared to long-lived vaccines, such as the yellow fever vaccine. Although worldwide vaccination campaigns have saved lives estimated in the tens of millions, side effects, ranging from mild reactogenicity to rare severe diseases, have been reported. This review provides an overview and mechanistic insights into immune responses and adverse effects documented primarily for COVID-19 mRNA vaccines. Furthermore, we discuss the perspectives of this promising vaccine platform and the challenges in balancing immunogenicity and adverse effects. [...] Recently, approved mRNA vaccines for COVID-19 from Pfizer/BioNTech and Moderna employed similar technological paths by utilizing antigenic mRNA encoding a nucleoside-modified prefusion form of the spike antigen (S-2P) packaged in ionizable cationic LNPs for delivery. Both formulations resulted in the strong induction of protective immunity in animal models and human vaccinees13. The immune response triggered by COVID-19 mRNA is characterized by robust production of spike-binding and neutralizing antibodies, as well as intermediate levels of T-cell responses (Fig. 1). Notably, after the first vaccination, moderate innate immune responses, including antiviral and interferon responses, were observed, while much broader and stronger inflammatory responses, such as sharp increases in inflammatory monocytes and IFN-γ, were observed after the boost immunization24.