Advancing mRNA vaccines: A comprehensive review of design, delivery, and efficacy in infectious diseases

Abstract

The COVID-19 pandemic has highlighted the transformative potential of messenger RNA (mRNA) vaccines in biomedicine, thanks to their rapid design, scalable production, and strong immunogenicity. Nonetheless, their widespread adoption remains hindered by challenges related to sequence optimization, delivery efficiency, thermostability, and safety. This review systematically summarizes recent progress in mRNA vaccine development, including advances in molecular engineering, delivery platforms, adjuvant properties, and artificial intelligence (AI)-driven predictive modeling. It covers codon optimization, nucleoside modification, untranslated region (UTR) engineering, and novel structural formats such as self-amplifying and circular mRNAs. The review also compares various delivery systems-including lipid nanoparticles, cationic polymers, and virus-like particles-focusing on their physicochemical characteristics and translational applicability. Particular attention is given to the intrinsic adjuvant properties of mRNA molecules and their delivery vehicles, as well as strategies for incorporating exogenous adjuvants to modulate immune responses. Furthermore, the article provides a succinct overview of key preclinical and clinical advancements in mRNA vaccines targeting major infectious diseases (e.g., HIV, influenza, RSV, rabies) and tumor-associated antigens (e.g., HPV). This review is among the first to highlight breakthroughs in the application of AI for antigen screening, mRNA sequence optimization, lipid component selection, and vaccine stability prediction. Finally, the review addresses current platform limitations and proposes future directions for interdisciplinary collaboration, offering both theoretical insights and practical recommendations for the safe and effective implementation of next-generation mRNA vaccines.

Keywords: Delivery technologies; Sequence optimization; Vaccine efficacy; Vaccine immunogenicity; mRNA vaccines.