Knife’s edge: Balancing immunogenicity and reactogenicity in mRNA vaccines

Abstract

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.

mRNA vaccines: Understanding immune responses and adverse effects

Researchers must clarify all aspects of immune responses to and side effects of mRNA vaccines so that they can be used against multiple diseases. The COVID-19 pandemic drove mRNA vaccine development, with the accelerated rollout of Pfizer/BioNTech and Moderna vaccines. A team led by Eui Ho Kim (Institut Pasteur Korea, Seongnam) and Jae-Hwan Nam (Catholic University of Korea, Bucheon) reviewed understanding of mRNA vaccine immune responses using mainly data from COVID vaccinations. The first dose of these cost-effective life-saving vaccines stimulated a robust antibody response but boosters were needed to maintain strong immunity. Recent progress in activating antigen-specific B-cells will enable diversified mRNA vaccines that protect against multiple virus strains. Side effects are often related to vaccine components. Further fine-tuning of mRNA vaccines will reduce the excessive immune responses associated with adverse reactions.